Heterogeneity of alpha-Adrenergic Responsiveness in Vascular Smooth Muscle: Role of Receptor Subtypes and Receptor Reserve

  • N. A. Flavahan
  • P. M. Vanhoutte
Part of the The Receptors book series (REC)


The existence of receptor subtypes (including those of alpha- and beta-adrenergic receptors) is usually postulated when faced with results obtained with novel agonists or antagonists that cannot be explained within the existing framework of receptor classification (Ahlquist, 1980; McGrath, 1982). Once receptor subclassification has been proposed on a functional basis, attempts are then made to confirm the existence of the different subtypes by receptor binding studies or receptor isolation techniques. For example, 10 yr. after the existence of alpha-1 adrenergic receptors was suggested by functional studies, these receptor sites are thought to be macromolecular structures (molecular weight, 160,000 daltons) that traverse the plasma membrane and extend above the lipid surface (Venter et al., 1984a,b). Although we are close to understanding the molecular structure and biological environment of the alpha-1 adrenergic receptors, their relative importance in vascular smooth muscle, their relationship with the other subtype(s) of alpha-adrenergic receptors, and the basis for differential modulation of the réponses to alpha-1 and alpha-2 adrenergic receptor activation are unclear. This chapter attempts to clarify these issues.


Saphenous Vein Adrenergic Receptor Contractile Response Calcium Channel Antagonist Adrenergic Response 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Agrawal, D. K., Triggle, C. R., and Daniel, E. E. (1984) Pharmacological characterization of the postsynaptic alpha adrenoceptors in vascular smooth muscle from canine and rat mesenteric vascular beds. J. Pharmacol Exp. Ther. 229, 831–838.PubMedGoogle Scholar
  2. Ahlquist, R. P. (1980) Historical perspective: Classification of adrenoceptors. J. Auton. Pharmacol. 1, 101–106.PubMedGoogle Scholar
  3. Alabaster, V. A., Keir, R. F., and Peters, C. J. (1985) Comparison of activity of alpha-adrenoceptor agonists and antagonists in dog and rabbit saphenous vein. Naunyn Schmiedebergs Arch. Pharmacol. 330, 33–36.PubMedGoogle Scholar
  4. Amitai, G., Dale Brown, R., and Taylor, P. (1984) The relationship between alpha1-adrenergic receptor occupancy and the mobilization of intracellular calcium. J. Biol. Chem. 259, 12519–12527.PubMedGoogle Scholar
  5. Ariens, E. J. (1979) Receptors: From fiction to fact. Tr. Pharmacol. Sci. 1, 11–15.Google Scholar
  6. Ariens, E. J. and Simonis, A. M. (1976) Receptors and Receptor Mechanisms, in Beta-adrenoceptor Blocking Agents (Saxena, P. R. and Forsyth, R. P., eds.) North-Holland, Amsterdam.Google Scholar
  7. Arunlakshana, O. and Schild, H. O. (1959) Some quantitative uses of drug antagonists. Br. J. Pharmacol. 14, 48–58.Google Scholar
  8. Awad, R., Payne, R., and Deth, R. C. (1983) Alpha adrenergic receptor subtype associated with receptor binding, Ca++ influx, Ca++ release and contractile events in the rabbit aorta. J. Pharmacol. Exp. Ther. 227, 60–67.PubMedGoogle Scholar
  9. Bassenge, E., Holtz, J., Sommer, O., and Saeed, M. (1982) Vascular α-a-drenoceptors mediate coronary constrictions induced by norepinephrine (NE) and by sympathetic nerve stimulation. Circulation 66, 11–153 (abstract).Google Scholar
  10. Berridge, M. J. (1984) Inositol triphosphate and diacylglycerol as second messengers. Biochem. J. 220, 345–360.PubMedGoogle Scholar
  11. Bevan, J. A., Bevan, R. D., and Laner, I. (1985) Role of alpha-adrenoceptors in vascular control. Clin. Sci. 68 (suppl. 10), 83s–89s.PubMedGoogle Scholar
  12. Beckeringh, J. J., Thoolen, M. J. M. C, De Jonge, A., Wilffert, B., Timmermans, P. B. M. W. M., and van Zwieten, P. A. (1984a) Differential effects of the calcium entry blocker D600 on contractions of rat and guinea-pig aortas elicited by various alpha-1 adrenoceptor agonists. J. Pharmacol. Exp. Ther. 229, 515–521.PubMedGoogle Scholar
  13. Beckeringh, J. J., Thoolen, M. J. M. C, De Jonge, A., Wilffert, B., Timmermans, P. B. M. W. M., and van Zwieten, P. A. (1984b) The contractions induced in rat and guinea-pig aortic strips by the α-adrenoceptor selective agonists B-HT 920 and UK 14, 304 are mediated by α-adrenoceptors. Eur. J. Pharmacol. 104, 197–203.PubMedGoogle Scholar
  14. Bobik, A. (1982) Identification of alpha-adrenoceptor subtypes in dog arteries by 3H-yohimbine and 3H-prazosin. Life Sci. 30, 219–228.PubMedGoogle Scholar
  15. Burnstock, G. and Sneddon, P. (1985) Evidence for ATP and noradrenaline as cotransmitters in sympathetic nerves. Clin. Sci. 68, (suppl. 10), 89s–93s.PubMedGoogle Scholar
  16. Cauvin, C. and Malik, S. (1984) Induction of Ca++ influx and intracellular Ca++ release in isolated rat aorta and mesenteric resistance vessels by norepinephrine activation of alpha-1 receptors. J. Pharmacol. Exp. Ther. 230, 413–418.PubMedGoogle Scholar
  17. Cauvin, C, Loutzenhiser, R., Hwang, O., and van Breemen, C. (1982) Alpha1-adrenoceptors induce Ca influx and intracellular Ca release in isolated rabbit aorta. Eur. J. Pharmacol. 84, 233–235.PubMedGoogle Scholar
  18. Cauvin, C, Loutzenhiser, R., and van Breemen, C. (1983) Mechanisms of calcium antagonist-induced vasodilatation. Ann. Rev. Pharmacol. Toxicol. 23, 373–396.Google Scholar
  19. Cauvin, C, Saida, K., and van Breeman, C. (1984) Extracellular Ca2+ dependence and diltiazem inhibition of contraction in rabbit conduit arteries and mesenteric resistance vessels. Blood Vessels 21, 23–31.PubMedGoogle Scholar
  20. Cavero, I., Shepperson, N., Lefevre-Borg, F., and Langer, S. Z. (1983) Differential inhibition of vascular smooth muscle responses to alpha1-and alpha2-adrenoceptor agonists by diltiazem and verapamil. Circ. Res. 52 (suppl. I), 69–76.Google Scholar
  21. Cheung, D. W. (1982) Two components of the cellular response of rat tail arteries to nerve stimulation. J. Physiol. (Lond.) 328, 461–468.PubMedGoogle Scholar
  22. Cheung, D. W. (1984) An electrophysiological study of alpha-adrenoceptor mediated excitation contraction coupling in the smooth muscle cells of the rat saphenous vein. Br. J. Pharmacol. 84, 265–271.Google Scholar
  23. Cocks, T. M. and Angus, J. A. (1983) Endothelium-dependent relaxation of coronary arteries by noradrenaline and serotonin. Nature 305, 627–630.PubMedGoogle Scholar
  24. Cohen, R. A., Shepherd, J. T., and Vanhoutte, P. M. (1983) Prejunctional and postjunctional actions of endogenous norepinephrine at the sympathetic neuroeffector junction in canine coronary arteries. Circ. Res. 52, 16–25.PubMedGoogle Scholar
  25. Colucci, W. S., Gimbrone, M. A., and Alexander, R. W. (1984) Regulation of myocardial and vascular alpha-adrenergic receptor affinity. Effect of guanine nucleotides, cations, estrogens and catecholamine depletion. Circ. Res. 55, 78–88.PubMedGoogle Scholar
  26. Colucci, W. S., Brock, T. A., Gimbrone, M. A., and Alexander, R. W. (1985) Nonlinear relationship between alpha-adrenergic receptor occupancy and norepinephrine-stimulated calcium flux in cultured vascular smooth muscle cells. Mol. Pharmacol. 27, 517–524.PubMedGoogle Scholar
  27. Constantine, J. W., Weeks, R. A., and McShane, W. K. (1978). Prazosin and presynaptic alpha-receptors in the cardioaccelerator nerve of the dog. Eur. J. Pharmacol. 50, 51–60.PubMedGoogle Scholar
  28. Constantine, J. W., Lebel, W., and Archer, R. (1982) Functional postsynaptic alpha2- but not alpha1-adrenoceptors in dog saphenous vein exposed to phenoxybenzamine. Eur. J. Pharmacol. 85, 325–329.PubMedGoogle Scholar
  29. Cooke, J. P., Rimele, T. J., Flavahan, N. A., and Vanhoutte, P. M. (1985) Nimodipine and inhibition of alpha-adrenergic activation of the isolated canine saphenous vein. J. Pharmacol. Exp. Ther. 234, 598–602.PubMedGoogle Scholar
  30. Cooke, J. P., Flavahan, N. A., Shepherd, J. T., and Vanhoutte, P. M. (1986) Differential contribution of alpha1 and alpha2-adrenoceptors to contractile responses to norepinephrine in human limb arteries. Blood Vessels, in press (abstract).Google Scholar
  31. Decker, N. and Schwartz, J. (1985) Postjunctional alpha1 and alpha2-adre-noceptors in the coronaries of the perfused guinea-pig heart. J. Pharmacol. Exp. Ther. 232, 251–257.PubMedGoogle Scholar
  32. Decker, N., Ehrhardt, J. D., Leclerc, G., and Schwartz, J. (1984) Postjunctional alpha-adrenoceptors alpha1 and alpha2 subtypes in rat vasculature in vitro and in vivo. Naunyn Schmiedebergs Arch. Pharmacol. 326, 1–6.PubMedGoogle Scholar
  33. De Mey, J. and Vanhoutte, P. M. (1981) Uneven distribution of postjunctional alpha1 and alpha2-like adrenoceptors in canine arterial and venous smooth muscle. Circ. Res. 48, 875–884.PubMedGoogle Scholar
  34. De Mey, J. G. and Vanhoutte, P. M. (1982) Heterogeneous behavior of the canine arterial and venous wall: importance of the endothelium. Circ. Res. 51, 439–447.PubMedGoogle Scholar
  35. Docherty, J. R. (1983) An investigation of presynaptic α-adrenoceptor subtypes in the pithed rat. Br. J. Pharmacol. 78, 655–657.PubMedGoogle Scholar
  36. Docherty, J. R. and Hyland, L. (1985) Vascular alpha2-adrenoceptors can mediate nerve stimulation-evoked contractions. Clin. Sci. 68 (suppl. 10), 117s–121s.PubMedGoogle Scholar
  37. Docherty, J. R. and McGrath, J. C. (1980) A comparison of pre- and postjunctional potencies of several alpha-adrenoceptor agonists in the cardiovascular system and anococcygens of the rat. Evidence for two types of postjunctional alpha-adrenoceptor. Naunyn Schmiedebergs Arch. Pharmacol. 312, 107–116.PubMedGoogle Scholar
  38. Drew, G. M. (1985) What do antagonists tell us about alpha-adrenoceptors? Clin. Sci. 68 (suppl. 10), 15s–21s.PubMedGoogle Scholar
  39. Drew, G. M. and Whiting, S. B. (1979) Evidence for two distinct types of postsynaptic alpha-adrenoceptor in vascular smooth muscle in vivo. Br. J. Pharmacol. 67, 207–215.PubMedGoogle Scholar
  40. Ekblad, E., Edvinsson, L., Wahlestedt, C, Uddman, R., Hakanson, R., and Sundler, F. (1984) Neuropeptide Y co-exists and co-operates with noradrenaline in perivascular nerve fibers. Regul. Pept. 8, 225–235.PubMedGoogle Scholar
  41. Feletou, M. and Vanhoutte, P. M. (1985) Endothelium-derived relaxing factors) hyperpolarizes coronary vascular smooth muscle. Physiologist 48, 325 (abstract).Google Scholar
  42. Ferron, P. M., Banner, W., and Duckies, S. P. (1984) Lack of specific 3H-prazosin binding sites in dog and rabbit cerebral arteries. Life Sci. 35, 2169–2176.PubMedGoogle Scholar
  43. Flavahan, N. A. (1983) Alpha-adrenoceptor subtypes in the cardiovascular system. Ph.D. thesis, University of Glasgow.Google Scholar
  44. Flavahan, N. A. and McGrath, J. C. (1981a) An analysis of alpha1 and alpha2-adrenoceptor mediated pressor effects of adrenaline. Br. J. Pharmacol. 72, 519P (abstract).Google Scholar
  45. Flavahan, N. A. and McGrath, J. C. (1981b) Alpha1 and alpha2-adrenoceptor agonism is dependent on respiratory acid-base balance. Br. J. Pharmacol. 74, 804P (abstract).Google Scholar
  46. Flavahan, N. A. and McGrath, J. C. (1984) Are human vascular alpha-adrenoceptors atypical? J. Cardiovasc. Pharmacol. 6, 208–210.PubMedGoogle Scholar
  47. Flavahan, N. A. and Vanhoutte, P. M. (1986a) Alpha1 and alpha-adrenoceptor: Response coupling in canine saphenous and femoral veins. J. Pharmacol. Exp. Ther. 238, 131–138.PubMedGoogle Scholar
  48. Flavahan, N. A. and Vanhoutte, P. M. (1986b) The effect of cooling on alpha1- and alpha2-adrennergic responses in canine saphenous and femoral veins. J. Pharmacol. Exp. Ther. 238, 139–147.PubMedGoogle Scholar
  49. Flavahan, N. A., Rimele, T. J., Cooke, J. P., and Vanhoutte, P. M. (1984) Characterization of postjunctional alpha1- and alpha2-adrenoceptors activated by exogenous or nerve-released norepinephrine in the canine saphenous vein. J. Pharmacol. Exp. Ther. 230, 699–705.PubMedGoogle Scholar
  50. Flavahan, N. A., Lindblad, E. L. E., Verbeuren, T. J., Shepherd, J. T., and Vanhoutte, P. M., (1985a) Cooling and alpha1 and alpha2-adrenergic responses in cutaneous veins: role of receptor-reserve. Am. J. Physiol. 249, H950–H955.PubMedGoogle Scholar
  51. Flavahan, N. A., Grant, T. L., Greig, T., and McGrath, J. C. (1985b) Analysis of the alpha-adrenoceptor-mediated, and other components in the sympathetic vasopressor responses of the pithed rat. Br. J. Pharmacol. 86, 265–274.PubMedGoogle Scholar
  52. Flavahan, N. A., Miller, V. M., and Vanhoutte, P. M. (1985c) Denervation augments alpha2- but not alphara1-arenergic responses in canine saphenous veins. Physiologist 48, 308.Google Scholar
  53. Fowler, P. J., Grous, M., Price, W., and Matthews, W. D. (1984) Pharmacological differentiation of postsynaptic alpha-adrenoceptors in the dog saphenous vein. J. Pharmacol. Exp. Ther. 229, 712–718.PubMedGoogle Scholar
  54. Furchgott, R. F. (1966) The use of β-haloalkylamines in the differentiation of receptors and in the determination of dissociation constants of receptor agonist complexes. Adv. Drug Res. 3, 21–55.Google Scholar
  55. Furchgott, R. F. (1983) Role of endothelium in responses of vascular smooth muscle. Circ. Res. 53, 557–573.PubMedGoogle Scholar
  56. Gardiner, J. C. and Peters, C. J. (1982) Postsynaptic alpha1- and alpha2-adrenoceptor involvement in the vascular responses to neuronally released and exogenous noradrenaline in the hindlimb of the dog and cat. Eur. J. Pharmacol. 84, 189–198.PubMedGoogle Scholar
  57. Gisclard, V., Flavahan, N. A., and Vanhoutte, P. M. (1986) Alpha-adrener-gic responses of blood vessels of rabbits after ovariectomy and administration of 17 β-estradiol. J. Pharmacol. Exp. Ther., in review.Google Scholar
  58. Glusa, E. and Markwardt, F. (1983) Characterization of postjunctional alpha-adrenoceptors in isolated human femoral veins and arteries. Naunyn Schmiedebergs Arch. Pharmacol. 323, 101–105.PubMedGoogle Scholar
  59. Godfraind, T., Miller, R. C, and Lima, J. S. (1982) Selective alpha-1 and alpha-2 adrenoceptor agonist induced contractions and 45Ca fluxes in the rat isolated aorta. Br. J. Pharmacol. 77, 597–602.PubMedGoogle Scholar
  60. Griendling, K. K., Sastre, A., and Milnor, W. R. (1984) Regional differences in alpha1-adrenoceptor numbers and responses in canine aorta. Am. J. Physiol. 247, H928–H935.PubMedGoogle Scholar
  61. Hausier, G. and De Peyer, J. E. (1985) Electrical membrane events in response to alpha-adrenoceptor stimulation. Clin. Sci. 68 (suppl. 10), 51s–53s.Google Scholar
  62. Hieble, J. P. and Woodward, D. F. (1984) Different characteristics of postjunctional alpha-adrenoceptors on arterial and venous smooth muscle. Naunyn Schmiedebergs Arch. Pharmacol. 328, 44–50.PubMedGoogle Scholar
  63. Hirst, G. D. S. and Neild, T. O. (1980) Evidence for two populations of excitatory receptors for noradrenaline on arterial smooth muscle. Nature 283, 767–768.PubMedGoogle Scholar
  64. Hirst, G. D. S. and Neild, T. O. (1981) Localization of specialised noradrenaline receptors at neuromuscular junctions on arterioles of the guinea-pig. J. Physiol. (Lond.) 313, 343–350.PubMedGoogle Scholar
  65. Hirst, G. D. S. and Neild, T. O. (1982) On the mechanism of action of prazosin at the sympathetic nerve muscle junction of arterioles of the guinea-pig Br. J. Pharmacol. 74, 189P (abstract).Google Scholar
  66. Hoick, M. I., Jones, C. H. M., and Haeusler, G. (1983) Differential interactions of Clonidine and methoxamine with the postsynaptic α-adreno-ceptor of rabbit main pulmonary artery. J. Cardiovasc. Pharmacol. 5, 240–248.Google Scholar
  67. Holman, M. E. and Surprenant A. (1980) An electrophysiological analysis of the effects of noradrenaline and alpha-receptor antagonists on neuromuscular transmission in mammalian muscular arteries. Br. J. Pharmacol. 71, 651–661.Google Scholar
  68. Holtz, J., Saeed, M., Sommer, O., and Bassenge, E. (1982) Norepinephrine constricts the canine coronary bed via postsynaptic α-adrenoceptors. Eur. J. Pharmacol. 82, 199–202.PubMedGoogle Scholar
  69. Itoh, T., Kitamura, K., and Kuriyama, H. (1983) Roles of extrajunctional receptors in the response of guinea-pig mesenteric and rat tail arteries to adrenergic nerves. J. Physiol. (Lond.) 345, 409–422.PubMedGoogle Scholar
  70. Janssens, W. J. and Vanhoutte, P. M. (1978) Instantaneous changes of alpha-adrenoceptor affinity caused by moderate cooling in canine cutaneous veins. Am. J. Physiol. 234, H330–H337.PubMedGoogle Scholar
  71. Janssens, W. and Verhaeghe, R. (1984) Sources of calcium used during α1 and α2-adrenergic contractions in canine saphenous veins. J. Physiol. (Lond.) 347, 525–532.PubMedGoogle Scholar
  72. Jim, K. F. and Matthews, W. D. (1985) Role of extracellular calcium in contractions produced by activation of postsynaptic alpha2-adrenoceptors in the canine saphenous vein. J. Pharmacol. Exp. Ther. 234, 161–165.PubMedGoogle Scholar
  73. Jim, K. F., De Marinis, R. M., and Matthews, W. D. (1985) Measurements of 45Ca2+ uptake and contractile responses after activation of postsynaptic alpha1-adrenoceptors in the isolated canine saphenous vein: Effects of calcium entry blockade. Eur. J. Pharmacol. 107, 199–208.PubMedGoogle Scholar
  74. Kenakin, T. P. (1984a) The classification of drugs and drug receptors in isolated tisssues. Pharmacol. Rev. 36, 165–222.PubMedGoogle Scholar
  75. Kenakin, T. P. (1984b) The relative contribution of affinity and efficacy to agonist activity: Organ selectivity of noradrenaline and oxymetazoline with reference to the classification of drug receptors. Br. J. Pharmacol. 81, 131–141.PubMedGoogle Scholar
  76. Kobayashi, H., Wada, A., Izumi, F., Magnoni, M.S., and Trabucchi, M. (1985) Alpha-adrenergic receptors in cerebral microvessels of normotenisve and spontaneously hypertensive rats. Circ. Res. 56, 402–409.PubMedGoogle Scholar
  77. Korstanje, C, Mathy, M. J., van Charldorp, K., de Jonge, A., and van Zwieten, P. A. (1985) Influence of respiratory acidosis or alkalosis on pressor responses mediated by alpha1 and alpha2-adrenoceptors in pithed normotensive rats. Naunyn Schmiedebergs Arch. Pharmacol. 330, 187–192.PubMedGoogle Scholar
  78. Kou, K., Ibengwe, J., and Suzuki, H. (1984) Effects of alpha-adrenoceptor antagonists on electrical and mechanical responses of the isolated dog mesenteric vein to perivascular nerve stimulation and exogenous noradrenaline. Naunyn Schmiedebergs Arch. Pharmacol. 326, 7–13.PubMedGoogle Scholar
  79. Laher, I. and Bevan, J. A. (1985) Alpha-adrenoceptor number limits response of some rabbit arteries to norepinephrine. J. Pharmacol. Exp. Ther. 233, 290–297.PubMedGoogle Scholar
  80. Langer, S. Z. and Shepperson, N. B. (1982) Postjunctional alpha1- and alpha2-adrenoceptors: Preferential innervation of alpha1-adrenoceptors and the role of neuronal uptake. J. Cardiovasc. Pharmacol. 4, S8–S13.PubMedGoogle Scholar
  81. Langer, S. Z., Massingham, R., and Shepperson, N. B. (1980) Presence of post-synaptic alpha2-adrenoceptors of predominantly extrasynaptic location in the vascular smooth muscle of the dog hind-limb. Clin. Sci. 59, 225s–228s.PubMedGoogle Scholar
  82. Lefkowitz, R. J., Caron, M. G., and Stiles, G. L. (1984) Mechanisms of membrane-receptor regulation. N. Engl. J. Med. 310, 1570–1579.PubMedGoogle Scholar
  83. Leijten, P., Cauvin, C, Lodge, N., Saida, K., and Van Breemen, C. (1985) Ca2+ sources mobilized by α1-receptor activation in vascular smooth muscle. Clin. Sci. 68 (suppl. 10), 47s–50s.PubMedGoogle Scholar
  84. Levitt, B. and Hieble, J. P. (1985) Characterization of pre- and postjunctional alpha-adrenoceptors in rabbit lateral saphenous vein. Fed. Proc. 44,1465 (abstract).Google Scholar
  85. Lorenz, R. R., Vanhoutte, P. M., and Shepherd, J. T. (1979) Interaction between neuronal amine uptake and prejunctional alpha-adrenergic receptor activation in smooth muscle from canine blood vessels and spleen. Blood Vessels 16, 113–125.PubMedGoogle Scholar
  86. Lundberg, J. M., Hokfelt, T., Anggard, A., Lundblad, L., Soria, A., Fahrenkrug, J., and Terenius, L. (1984) Neuropeptides with Vascular Activity: VIP, PHI, NPY and Substance P, in Vasodilator Mechanisms (Vanhoutte, P. M. and Vatner, S. F. eds.) Karger, Basel.Google Scholar
  87. Makita, Y. (1983) Effects of adrenoceptor agonists and antagonists on smooth muscle cells and neuromuscular transmission in the guinea-pig renal artery and vein. Br. J. Pharmacol. 80, 671–679.PubMedGoogle Scholar
  88. Manzini, S., Maggi, C. A., and Meli, A. (1983) Alpha-adrenoceptor subtypes and Ca2+ mobilization in the rabbit ear artery. J. Pharm. Pharmacol. 35, 584–589.PubMedGoogle Scholar
  89. Matthews, W. D., Macia, R. A., Beckeringh, J. J., De Marinis, R. M., de Jonge, A., Thoolen, M. J. M. C, Wilffert, B., Timmermans, P. B. M. W. M., and van Zwieten, P. A. (1984a) Calcium utilization in the vasoconstriction to enantiomers of S. K. and F 89748-A. J. Pharmacol. Exp. Ther. 232, 330–336.Google Scholar
  90. Matthews, W. D., McCafferty, G. P., and Grous, M. (1984b) Characterization of alpha-adrenoceptors on vascular smooth muscle: Electrophysiological differentiation in canine saphenous vein. J. Pharmacol. Exp. Ther. 231, 355–360.PubMedGoogle Scholar
  91. Matthews, W. D., Jim, K. F., Hieble, J. P., and De Marinis, R. M. (1984c) Postsynaptic α-adrenoceptors on vascular smooth muscle. Fed. Proc. 43, 2923–2928.PubMedGoogle Scholar
  92. McGrath, J. C. (1985) Alpha-adrenoceptor agonist and the Ca2+ -dependence of smooth muscle contraction: Evidence for subtypes of receptors or for agonist-dependent differences in the agonist-receptor interaction. Clin. Sci. 68 (suppl. 10), 55s–65s.PubMedGoogle Scholar
  93. McGrath, J. C. and Stuart-Smith, K. (1982) Human umbilical artery is contracted by oxygen, KCl or 5-HT but not by alpha-adrenergic agonists. Br. J. Pharmacol. 76, 258P (abstract).Google Scholar
  94. McGrath, J. C. (1982) Evidence for more than one type of postjunctional alpha-adrenoceptor. Biochem. Pharmacol. 31, 467–484.PubMedGoogle Scholar
  95. McGrath, J. C, Flavahan, N. A., and McKean, C. E. (1982) Alpha1- and al-pha2-adrenoceptor mediated pressor and chronotropic effects in the rat and rabbit. J. Cardiovasc. Pharmacol. 4, S101–S107.PubMedGoogle Scholar
  96. Medgett, I. C. (1985) Alpha2-adrenoceptors mediate sympathetic vasoconstriction in distal segments of rat tail artery. Eur. J. Pharmacol. 108, 281–287.PubMedGoogle Scholar
  97. Medgett, I. C. and Langer, S. Z. (1983) Characterization of smooth muscle alpha-adrenoceptors and of responses to electrical stimulation in cat isolated perfused middle cerebral artery. Naunyn Schmiedebergs Arch. Pharmacol. 323, 24–32.PubMedGoogle Scholar
  98. Medgett, I. C. and Langer, S. Z. (1984) Heterogeneity of smooth muscle alpha-adrenocepters in rat tail artery in vitro. J. Pharmacol. Exp. Ther. 229, 823–830.PubMedGoogle Scholar
  99. Meldrum, L. A. and Burnstock, G. (1983) Evidence that ATP acts as a co-transmitter with noradrenaline in sympathetic nerves supplying the guinea-pig vas deferens. Eur. J. Pharmacol. 92, 161–163.PubMedGoogle Scholar
  100. Michell, R. H. (1985) Inositol lipid breakdown as a step in alpha-adrenergic stimulus-response coupling. Clin. Sci. 68 (suppl. 10), 43s–47s.PubMedGoogle Scholar
  101. Miller, V. M. and Vanhoutte, P. M. (1985) Endothelial alpha2-adrenoceptors in canine pulmonary and systemic blood vessels. Eur. J. Pharmacol 118, 123–129.PubMedGoogle Scholar
  102. Miller, V. M. and Vanhoutte, P. M. (1986) Modulation of endothelium-dependent responses by chronic alterations of blood flow. Am. J. Physiol., in review.Google Scholar
  103. Muller-Schweinitzer, E. (1983) Tissue specific susceptibility of alpha-adreno-ceptor mediated vasoconstriction to nifedipine. Naunyn Schmiedebergs Arch. Pharmacol. 324, 64–69.PubMedGoogle Scholar
  104. Nahorski, S. R., Barnett, D. B., and Cheung, Y. D. (1985) Alpha-adrenoceptor-effector coupling: Affinity states or heterogeneity of the alpha2-adrenoceptor? Clin. Sci. 68 (suppl. 10), 39s–43s.PubMedGoogle Scholar
  105. Neild, T. O. and Zelcer, E. (1982) Noradrenergic neuromuscular transmission with special reference to arterial smooth muscle. Prog. Neurobiol. 19, 141–158.PubMedGoogle Scholar
  106. O’Brien, J. W., Flavahan, N. A., Grant, T. L., McGrath, J. C, and Marshall, R. J. (1985) Influence of blood gases, Ca2+-entry blockade and angiotensin converting enzyme inhibition on pressor responses to Ta-adrenoceptor agonists: Evidence in vivo for subtypes of response independent of receptor subtype? Clin. Sci. 68 (suppl. 10), 99s–105s.PubMedGoogle Scholar
  107. Pedrinelli, R. and Tarazi, R. C. (1984) Interference of calcium entry blockade in vivo with pressor responses to alpha-adrenergic stimulation: Effects of two unrelated blockers on responses to both exogenous and endoge-nously released norepinephrine. Circulation 69, 1171–1176.PubMedGoogle Scholar
  108. Pedrinelli, R. and Tarazi, R. C. (1985a) Calcium entry blockade by nitrendipine and alpha adrenergic responsiveness in vivo: Comparison with noncalcium entry blocker vasodilators in absence and presence of phenoxybenzamine treatment. J. Pharmacol. Exp. Ther. 233, 636–643.PubMedGoogle Scholar
  109. Pedrinelli, R. and Tarazi, R. C. (1985b) Calcium entry blockade by nitrendipine and alpha adrenergic responsiveness in vivo: Comparison of systemic vs. local effects. J. Pharmacol. Exp. Ther. 233, 643–649.PubMedGoogle Scholar
  110. Polonia, J. J., Paiva, M. Q., and Guimaraes, S. (1984) Pharmacological characterization of postsynaptic alpha-adrenoceptor subtypes in five different dog arteries in vivo. J. Pharm. Pharmacol. 32, 205–208.Google Scholar
  111. Purdy, R. E. and Stupecky, G. L. (1984) Characterization of the alpha-adrenergic receptor properties of rabbit ear artery and thoracic aorta. J. Pharmacol. Exp. Ther. 229, 459–468.PubMedGoogle Scholar
  112. Purdy, R. E., Ashbrook, D. W., Stupecky, G. L., and Watanabe, M. Y. (1983) Qualitative and quantitative differences between the postsynaptic alpha-adrenoceptors of rabbit ear artery and thoracic aorta. J. Pharmacol Exp. Ther. 224, 543–551.PubMedGoogle Scholar
  113. Rimele, T. J., Rooke, T. W., Aarhus, L. L., and Vanhoutte, P. M. (1983) Alpha-adrenoceptors and calcium in isolated canine coronary arteries. J. Pharmacol Exp. Ther. 226, 668–672.PubMedGoogle Scholar
  114. Rosendorff, C, U’Prichard, D. C, and Hurwitz, M. L. (1981) Alpha-nora-drenergic receptor binding sites in bovine aorta. Basic Res. Cardiol. 76, 536–539.PubMedGoogle Scholar
  115. Rubanyi, G. M., Lorenz, R. R., and Vanhoutte, P. M. (1985) Bioassay of endothelium-derived relaxing factor(s). Inactivation by catecholamines. Am. J. Physiol. 249, H95–H101, 1985.PubMedGoogle Scholar
  116. Ruffolo, R. R. (1985) Relative agonist potency as a means of differentiating alpha-adrenoceptors and adrenergic mechanisms. Clin. Sci. 68 (suppl. 10), 9s–14s.PubMedGoogle Scholar
  117. Ruffolo, R. R. and Yaden, E. L. (1984) Existence of spare alpha1-adrenocep-tors, but not alpha2-adrenoceptors, for respective vasopressor effects of cirazoline and B-HT 933 in the pithed rat. J. Cardiovasc. Pharmacol. 6, 1011–1019.PubMedGoogle Scholar
  118. Ruffolo, R. R. Jr. and Zeid, R. L. (1985) Relationship between alpha-adrenoceptor occupancy and response for the alpha-1 adrenoceptor agonist, cirazoline, and the alpha-2 adrenoceptor agonist, B-HT 933, in canine saphenous vein. J. Pharmacol. Exp. Ther. 235, 636–643.PubMedGoogle Scholar
  119. Ruffolo, R. R., Waddell, J. E., and Yaden, E. L. (1981) Postsynaptic alpha adrenergic receptor subtypes differentiated by yohimbine in tissues from the rat. Existence of alpha-2 adrenergic receptors in rat aorta. J. Pharmacol. Exp. Ther. 217, 235–240.PubMedGoogle Scholar
  120. Ruffolo, R. R., Waddell, J. R., and Yaden, E. L. (1982) Heterogeneity of post-synaptic alpha-adrenoceptors in mammalian aortas. J. Pharmacol. Exp. Ther. 221, 309–314.PubMedGoogle Scholar
  121. Ruffolo, R. R., Morgan, E. L., and Messick, K. (1984) Possible relationship between receptor reserve and the differential antagonism of alpha-1 and alpha-2 adrenoceptor mediated pressor responses by calcium channel antagonists in the pithed rat. J. Pharmacol. Exp. Ther. 230, 587–594.PubMedGoogle Scholar
  122. Saeed, M., Holtz, J., Eisner, D., and Bassenge, E. (1983) Attenuation of sympathetic vasoconstriction by nifedipine: the role of alpha2-adreno-ceptors. Eur. J. Pharmacol. 94, 149–153.PubMedGoogle Scholar
  123. Sakakibara, Y., Fujiwara, M., and Muramatsu, I. (1982) Pharmacological characterization of the alpha-adrenoceptors of the dog basilar artery. Naunyn Schmiedebergs Arch. Pharmacol. 319, 1–7.PubMedGoogle Scholar
  124. Sastre, A., Griendling, K. K., Rusher, M. M., and Milnor, W. R. (1984) Relation between alpha-adrenergic receptor occupation and contractile response: Radioligand and physiologic studies in canine aorta. J. Pharmacol. Exp. Ther. 229, 887–896.PubMedGoogle Scholar
  125. Shepherd, J. T. and Vanhoutte, P. M. (1985) Local modulation of adrenergic neurotransmission in blood vessels. J. Cardiovasc. Pharmacol. 7 (suppl. 3), S167–S178.PubMedGoogle Scholar
  126. Shepperson, N. B. and Langer, S. Z. (1981) The effects of the 2-amino-tetrahydronaphthalene derivative M7, a selctive alpha2-adrenoceptor agonist in vitro. Naunyn Schmiedebergs Arch. Pharmacol. 318, 10–13.PubMedGoogle Scholar
  127. Skarby, T. V. C, Andersson, K. E., and Edvinsson, L. (1983) Pharmacological characterization of postjunctional alpha-adrenoceptors in isolated feline cerebral and peripheral arteries. Acta Physiol. Scand. 117, 63–73.PubMedGoogle Scholar
  128. Sneddon, P., Westfall, D. P., and Fedan, J. S. (1982) Co-transmitters in the motor nerves of the guinea-pig vas deferns: Electrophysiological evidence. Science 218, 693–695.PubMedGoogle Scholar
  129. Sneddon, P. and Bunstock, A. (1984) ATP as a neurotransmitter in rat tail artery. Eur. J. Pharmacol. 106, 149–152.PubMedGoogle Scholar
  130. Starke, K. (1972) Alpha sympathomimetic inhibition of adrenergic and cholinergic transmission in the rabbit heart. Naunyn Schmiedebergs Arch. Pharmacol. 274, 18–45.PubMedGoogle Scholar
  131. Starke, K. (1977) Regulation of noradrenaline release by presynaptic receptor systems. Rev. Physiol. Biochem. Pharmacol. 77, 1–124.PubMedGoogle Scholar
  132. Steen, S., Sjoberg, T., Skarby, T., Norgren, L., and Andersson, K. -E. (1984a) The postjunctional alpha-adrenoceptors of the human saphenous vein. Acta Pharmacol. Toxicol. 55, 351–357.Google Scholar
  133. Steen, S., Sjoberg, T., Skarby, T., Norgren, L., and Andersson, K. -E. (1984b) Postjunctional alpha1-and alpha2-adrenoceptors mediating contraction in isolated human groin arteries and veins. Acta Physiol Scand. 122 323–329.PubMedGoogle Scholar
  134. Steen, S., Skarby, T. V. C, Norgren, L., and Andersson, K. -E. (1984c) Pharmacological characterization of postjunctional alpha-adrenoceptors in isolated human omental arteries and veins. Acta Physiol. Scand. 120, 109–116.PubMedGoogle Scholar
  135. Stevens, M. J. and Moulds, R. F. W. (1982) Are the pre- and postsynaptic alpha-adrenoceptors in human vascular smooth muscle atypical? J. Cardiovasc. Pharmacol. 4, S129–S133.PubMedGoogle Scholar
  136. Stevens, M. J. and Moulds, R. F. W. (1985) Neuronally-released norepinephrine does not preferentially activate postjunctional alpha1-adrenoceptors in human blood vessels in vitro. Circ. Res. 57, 399–406.PubMedGoogle Scholar
  137. Story, D. F., Standford-Starr, C. A., and Rand, M. J. (1985) Evidence for the involvement of alpha1-adrenoceptors in negative feedback regulation of noradrenergic transmitter release in rat atria. Clin. Sci. 68 (suppl. 10), 111s–117s.PubMedGoogle Scholar
  138. Sullivan, A. T. and Drew, G. M. (1980) Pharmacological characterization of pre- and postsynaptic alpha-adrenoceptors in dog saphenous vein. Naunyn Schmiedebergs Arch. Pharmacol. 314, 249–258.Google Scholar
  139. Suzuki, H. (1981) Effects of endogenous and exogenous noradrenaline on the smooth muscle of guinea-pig mesenteric vein. J. Physiol. (Lond.) 321, 495–512.PubMedGoogle Scholar
  140. Suzuki, H. (1983) An electrophysiological study of excitatory neuromuscular transmission in the guinea-pig main pulmonary artery. J. Physiol. (Lond.) 336, 47,59.Google Scholar
  141. Suzuki, H. and Kou, K. (1983) Electrical components contributing to the nerve mediated contractions in the smooth muscle of the rabbit ear artery. Jpn. J. Physiol. 33, 745–758.Google Scholar
  142. Tayo, F. M., Bevan, R. D., and Bevan, J. A. (1985) Changes in postjunctional alpha-adrenoceptors during postnatal growth in rabbit arteries. Fed. Proc. 44, 1465 (abstract).Google Scholar
  143. Timmermans, P. B. M. W. M. and van Zwieten, P. A. (1982) Alpha2-adrenoceptors: classification, localization, mechanisms, and targets for drugs. J. Med. Chem. 25, 1389–1401.PubMedGoogle Scholar
  144. Timmermans, P. B. M. W. M., Thoolen, J. J. M. C, Mathy, M. J., Wilffert, B., De Jonge, A., and van Zwieten, P. A. (1983a) Sgd 101/75 is distinguished from other selective alpha-1 adrenoceptor agonists by the inhibition of its pressor responses by calcium entry blockade and vasodilatation in pithed rats and cats. Eur. J. Pharmacol. 96, 187–192.PubMedGoogle Scholar
  145. Timmermans, P. B. M. W. M., Mathy, M. J., Wilffert, B., Kalkman, H. O., Thoolen, M. J. M. C, De Jonge, A., Van Meel, J. C. A., and van Zwieten, P. A. (1983b) Differential effect of calcium entry blockers on alpha-1 adrenoceptor mediated vasoconstriction in vivo. Naunyn Schmiedebergs Arch. Pharmacol. 324, 239–245.PubMedGoogle Scholar
  146. Timmermans, P. B. M. W. M., Thoolen, M. J. M. C, De Jonge, A., Wilffert, B., and van Zwieten, P. A. (1985a) Functional consequences of contrasting properties of alpha-1/alpha-2 systems. Clin. Sci. 68 (suppl. 10), 93s–97s.PubMedGoogle Scholar
  147. Timmermans, P. B. M. W. M., Thoolen, M. J. M. C, Mathy, M. J., Wilffert, B., De Jonge, A., and van Zwieten, P. A. (1985b) Effect of the irreversible α-adrenoceptor antagonists phenoxybenzamine and benextramine on the effectiveness of nifedipine in inhibiting α 1 and α2-adrenoceptor mediated vasoconstriction in pithed rats. Naunyn Schmiedebergs Arch. Pharmacol. 329, 404–413.PubMedGoogle Scholar
  148. Van Breemen, C, Hwang, O., and Meisheri, K. D. (1981) The mechanism of inhibitory action of diltiazem on vascular smooth muscle contractility. J. Pharmacol. Exp. Ther. 218, 459–464.PubMedGoogle Scholar
  149. Vanhoutte, P. M. and Flavahan, N. A. (1986) Effects of temperature on α-adrenoceptors in limb veins: Role of receptor-reserve. Fed. Proc, in press.Google Scholar
  150. Vanhoutte, P. M. (1980) Physical Factors and Regulation of Vascular Smooth Muscle Function, in Handbook of Physiology section 2. Circulation vol. II. Vascular Smooth Muscle (Bohr, D. F., Somlyg, A. P., and Sparks, H. V., eds.) The American Physiological Society, Washington, DC.Google Scholar
  151. Vanhoutte, P. and Lorenz, R. R. (1970) Effect of temperature on the reactivity of saphenous, mesenteric, and femoral veins of the dog. Am. J. Physiol. 218, 1746–1750.PubMedGoogle Scholar
  152. Vanhoutte, P. and Shepherd, J. T. (1970) Effect of temperature on reactivity of isolated cutaneous veins of the dog. Am. J. Physiol. 218, 187–190.PubMedGoogle Scholar
  153. Vanhoutte, P. M. and Rimele, T. J. (1982) Calcium and α-adrenoceptors in activation of vascular smooth muscle. J. Cardiovasc. Pharmacol. 4, S280–S286.PubMedGoogle Scholar
  154. Vanhoutte, P. M., Verbeuren, T. J., and Webb, R. C. (1981) Local modulation of the adrenergic neuroeffector interaction in the blood vessel wall. Physiol. Rev. 61, 151–247.PubMedGoogle Scholar
  155. Vanhoutte, P. M., Rubanyi, G. M., Miller, V. M., and Houston, D. S. (1986) Modulation of vascular smooth muscle contraction by the endothelium. Ann. Rev. Physiol. 48, 307–320.Google Scholar
  156. Van Meel, J. C. A., De Jonge, A., Kalkman, H. O., Wilffert, B., Timmermans, P. B. M. W. M., and van Zwieten, P. A. (1981) Organic and inorganic calcium antagonists reduce vasoconstriction in vivo mediated by postsynaptic alpha-2 adrenoceptors. Naunyn Schmiedebergs Arch. Pharmacol. 316, 288–293.PubMedGoogle Scholar
  157. Van Meel, J. C. A., Wilffert, B., De Zoeten, K., Timmermans, P. B. M. W. M., and van Zwieten, P. A. (1982) The inhibitory effect of newer calcium antagonists (nimodipine and PY-108–068) on vasoconstriction in vivo mediated by postsynaptic alpha2-adrenoceptors. Arch. Int. Pharmacodyn. 260, 206–217.PubMedGoogle Scholar
  158. van Zwieten, P. A., Van Meel, J. C. A., and Timmermans, P. B. M. W. M. (1982) Ca++ antagonists and alpha2-adrenoceptors: Possible role of extracellular calcium ions in alpha2-adrenoceptor mediated vasconstric-tion. J. Cardiovasc. Pharmacol. 4, S273–S279.PubMedGoogle Scholar
  159. van Zwieten, P. A., Van Meel, J. C. A., and Timmermans, P. B. M. W. M. (1983a) Functional interaction between calcium antagonists and the vasconstriction induced by stimulation of postsynaptic alpha2-adreno-ceptors. Circ. Res. 52 (suppl. 1), 77–80.Google Scholar
  160. van Zwieten, P. A., Van Meel, J. C. A., and Timmermans, P. B. M. W. M. (1983b) Pharmacology of calcium entry blockers: Interaction with vascular alpha-adrenoceptors. Hypertension 5 (suppl. II), II8-II17.Google Scholar
  161. Venter, J. C, Berzofsky, J. A., Lindstrom, J., Jacobs, S., Fraser, C. M., Kohn, L. D., Schneider, W. J., Greene, G. L., Strosberg, A. D. and Erlanger, B. F. (1984b) Monoclonal and anti-idiotypic antibodies as probes for receptor structure and function. Fed. Proc. 43, 2532–2539.PubMedGoogle Scholar
  162. Ventor, J. C., and Home, P., Greguski, R., and Fraser, C. M. (1984a) Alpha1-adrenergic receptor structure. Mol. Pharmacol. 26, 196–205.Google Scholar
  163. Wahlestedt, C., Edvinsson, L., Ekblad, E., and Hakanson, R. (1985) Neuropeptide Y potentiates noradrenaline-evoked vasoconstriction: Mode of action. J. Pharmacol. Exp. Ther. 234, 735–741.PubMedGoogle Scholar
  164. Wilffert, B., Timmermans, P. B. M. W. M., and van Zwieten, P. A. (1982a) Extrasynaptic location of alpha2- and non-innervated beta2-adrenocep-tors in the vascular system of the pithed normotensive rat. J. Pharmacol. Exp. Ther. 221, 762–768.PubMedGoogle Scholar
  165. Wilffert, B., Gouw, M. A. M., De Jonge, A., Timmermans, P. B. M. W. M., and van Zwieten, P. A. (1982b) Indications for vascular alpha- and beta-2 adrenoceptors in synapses of the muscarinic pathway in the pithed normo-tensive rat. J. Pharmacol. Exp. Ther. 223, 219–223.PubMedGoogle Scholar
  166. Yamaguchi, I. and Kopin, I. J. (1980) Differential inhibition of alpha1 and alpha2-adrenopceptor-mediated pressor responses in pithed rats. J. Pharmacol. Exp. Ther. 214, 275–281.PubMedGoogle Scholar

Copyright information

© The Humana Press Inc. 1987

Authors and Affiliations

  • N. A. Flavahan
  • P. M. Vanhoutte

There are no affiliations available

Personalised recommendations