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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 338, Issue 5, pp 529–535 | Cite as

Alpha-1 and alpha-2 adrenoceptor agonists induce vasoconstriction of the normotensive rat caudal artery in vitro by stimulation of a heterogeneous population of alpha-1 adrenoceptors

  • J. Atkinson
  • N. Trescases
  • C. Benedek
  • N. Boillat
  • A. K. Fouda
  • F. Krause
  • M. C. Pitton
  • C. Rafizadeh
  • J. C. de Rivaz
  • M. Saute
  • M. Sonnay
Article

Summary

Although alpha-2 adrenoceptor agonists rapidly induce arterial vasoconstriction in vivo, such responses have proven difficult to obtain in vitro. We have investigated the vasoconstrictor effects of various alpha-1 and alpha2 adrenoceptor agonists in the perfused/superfused caudal artery of the normotensive rat. Intrinsic activities were: methoxamine: 1, phenylephrine: 0.94, noradrenaline: 0.93, guanfacine: 0.88, clonidine: 0.47, UK 14,304 [5-bromo-6-(2imidazoline-2-ylamino)-quinoxaline tartrate: 0.10, azepexole: 0. Antagonism by the selective alpha-1 agent, prazosin of the vasoconstrictor responses provoked by methoxamine, guanfacine or clonidine, showed a high affinity with -log KB values in the range of 8.5 to 9.4. There were no significant differences between the KB values obtained with the three agonists. Antagonism by the selective alpha-2 antagonist, yohimbine showed a low affinity with KB values between 6.7 to 7.6 for the three agonists. The calcium entry blocker, nicardipine, antagonized responses to clonidine at nanomolar concentrations and those to phenylephrine at micromolar concentrations. We conclude that vasoconstrictor responses in this isolated tail artery preparation are primarily mediated via an alpha adrenoceptor which can be classified, on the basis of the results with specific antagonists, as being of the alpha-1 type. The results obtained with nicardipine suggest that the population of alpha adrenoceptors is not, however, homogeneous.

Key words

Alpha adrenoceptor agonists Rat tail artery Nicardipine 

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References

  1. Abrol RP, Hughes VM, Krueger CA, Cook DA (1984) Detection of endothelium in cerebral blood vessels. J Pharmacol Meth 12:213–219CrossRefGoogle Scholar
  2. Agrawal DK, Daniel EE (1985) Two distinct populations of [3H] prazosin and [3H] yohimbine binding sites in the plasma membrane of rat mesenteric artery. J Pharmacol Exp Ther 233:195–201PubMedGoogle Scholar
  3. Atkinson J, Boillat N, Fouda AK, Sonnay M (1986) Alpha adrenoceptors and vasoconstriction of the rat tail artery. Br J Pharmacol 88:451 PCrossRefGoogle Scholar
  4. Atkinson J, Boillat N, Fouda AK, Guillain H, Sautel M, Sonnay M (1987) Noradrenaline inhibits vasoconstriction induced by electrical stimulation. Gen Pharmacol 18:219–223CrossRefGoogle Scholar
  5. Atkinson J, Sonnay M, Sautel M, Fouda AK (1987) Chronic treatment of the spontaneously hypertensive rat with captopril attenuates responses to noradrenaline in vivo but not in vitro. Naunyn-Schmiedeberg's Arch Pharmacol 335:624–634CrossRefGoogle Scholar
  6. Beckeringh JJ, Thoolen MJMC, De Jonge A, Wilffert B, Timmermans PBMWM, Van Zwieten PA (1984) The contractions induced in rat and guinea pig aortic strips by the alpha-2 adrenoceptor selective agonists B-HT 920 and UK 14,304 are mediated by alpha-1 adrenoceptors. Eur J Pharmacol 104:197–203CrossRefGoogle Scholar
  7. Descombes JJ, Stoclet JC (1985) Characterization of two distinct alpha-adrenoceptor binding sites in smooth muscle cell membranes from rat and bovine aorta. Naunyn-Schmiedeberg's Arch Pharmacol 329:282–288CrossRefGoogle Scholar
  8. Digges KG, Summers RJ (1983) Effects of yohimbine stereoisomers on contractions of rat aortic strips produced by agonists with different selectivity for alpha-1 and alpha-2 adrenoceptors. Eur J Pharmacol 96:95–99CrossRefGoogle Scholar
  9. Fouda AK, Marazzi A, Boillat N, Guillain H, Atkinson J (1987) Changes in the vascular reactivity of the isolated tail arteries of spontaneous and renovascular hypertensive rats to endogenous and exogenous noradrenaline. Blood Vessels 24:63–75PubMedGoogle Scholar
  10. Furchgott RF (1972) The classification of adrenoceptors (adrenergic receptors). An evaluation from the standpoint of receptor theory. In: Blaschko H, Muscholl E (eds) Handbook of exp pharmacol, catecholamines, vol 33. Springer, Berlin Heidelberg New York, pp 283–335Google Scholar
  11. Haeusler G (1985) Contraction of vascular muscle as related to membrane potential and calcium fluxes. J Cardiovasc Pharmacol 7:S3-S8CrossRefGoogle Scholar
  12. Hicks PE, Tierney C, Langer SZ (1985) Preferential antagonism by diltiazem of alpha-2 adrenoceptor mediated vasoconstrictor responses in perfused tail arteries of spontaneous hypertensive rats. Naunyn-Schmiedeberg's Arch Pharmacol 328:388–395CrossRefGoogle Scholar
  13. Imbs JL, Krieger JP, Schmidt M, Giesen AM, Schwartz J (1984) Caractérisation des alpha adrénocepteurs du lit vasculaire du rein du rat isolé. Arch Mal C≸ur 77:1191–1194Google Scholar
  14. Kobinger W, Pischler L (1981) Alpha-2 adrenoceptor agonistic effect of B-HT 920 in isolated perfused hindquarter of rats. Eur J Pharmacol 76:101–105CrossRefGoogle Scholar
  15. Korstanje C, Mathy MJ, Van Charldorp K, De Jonge A, Van Zwieten PA (1985) Influence of respiratory acidosis or alcalosis on pressor responses mediated by alpha-1 and alpha-2 adrenoceptors in pithed normotensive rats. Naunyn-Schmiedeberg's Arch Pharmacol 330:187–192CrossRefGoogle Scholar
  16. Langer SZ, Hicks PE (1984) Alpha-adrenoceptor subtypes in blood vessels: physiology and pharmacology. J Cardiovasc Pharmacol 6:S547-S558CrossRefGoogle Scholar
  17. Langer SZ, Duval N, Massingham R (1985) Pharmacologic and therapeutic significance of alpha-adrenoceptor subtypes. J Cardiovasc Pharmacol 7:S1-S8PubMedGoogle Scholar
  18. Lues 1, Schümann HJ (1984) B-HT 920 acts as an alpha-1 adrenoceptor agonist in the rabbit aorta under certain in vitro conditions. Naunyn-Schmiedeberg's Arch Pharmacol 325: 42–46CrossRefGoogle Scholar
  19. Marcia RA, Matthews WD, Lafferty J, De Marinis RL (1984) Assessment of alpha-adrenergic receptor subtypes in isolated rat aortic segments. Naunyn-Schmiedeberg's Arch Pharmacol 325:306–309CrossRefGoogle Scholar
  20. Marwood JF, Chapman KL, Armsworth SJ, Stokes GS (1985) Investigations into the nature of alpha-2 adrenoceptors in rat tail arteries. Clin Exp Pharmacol Physiol 12:231–234CrossRefGoogle Scholar
  21. Marwood JF, Chapman KL, Stokes GS (1986) Studies that question the existence of alpha-2 adrenoceptors in tail arteries of normotensive Sprague-Dawley rats. J Pharmacol Exp Ther 238:267–272PubMedGoogle Scholar
  22. Matsuda H, Kuon E, Hotz J, Busse R (1985) Endothelium-mediated dilations contribute to the polarity of the arterial wall in vasomotion induced by alpha-2 adrenergic agonists. J Cardiovase Pharmacol 7:680–688CrossRefGoogle Scholar
  23. Medgett IC, Langer SZ (1984) Heterogeneity of smooth muscle alpha adrenoceptors in rat tail artery in vitro. J Pharmacol Exp Ther 229:823–829PubMedGoogle Scholar
  24. Medgett IC, Hicks PE, Langer SZ (1984) Smooth muscle alpha-2 adrenoceptors mediate vasoconstrictor responses to exogenous norepinephrine and to sympathetic stimulation to a greater extent in spontaneously hypertensive than in Wistar Kyoto rat tail arteries. J Pharmacol Exp Ther 231:159–165PubMedGoogle Scholar
  25. Megens AAHP, Leysen JE, Awouters FHL, Niemeggers CJE (1986) Further validation of in vivo and in vitro pharmacological procedures for assessing the alpha-2/alpha-1 selectivity of test compounds: (2) alpha adrenoceptor agonists. Eur J Pharmacol 129:57–64CrossRefGoogle Scholar
  26. Palluk R, Hoefke W, Gaida W (1985) Postjunctional alpha-adrenoceptors and influence of angiotensin II in different isolated blood vessels. Drug Res 35:395–401Google Scholar
  27. Ruffolo RR, Rosing EL, Waddell JE (1979) Receptor interactions of imidazolines. I. Affinity and efficacy for alpha adrenoceptor agonists in rat aorta. J Pharmacol Exp Ther 209:429–436PubMedGoogle Scholar
  28. Ruffolo RR, Waddell JE (1982) Receptor interactions of imidazolines: alpha-adrenoceptors of rat and rabbit aortae differentiated by relative potencies, affinities and efficacies of imidazoline agonists. Br J Pharmacol 77:169–176CrossRefGoogle Scholar
  29. Ruffolo RR (1985) Distribution and function of peripheral alpha-adrenoceptors in the cardiovascular system. Pharmacol Biochem Behav 22:827–833CrossRefGoogle Scholar
  30. Schümann HJ, Lues I (1983) Postjunctional alpha-adrenoceptors in the isolated saphenous vein of the rabbit. Characterization and influence of angiotensin. Naunyn-Schmiedeberg's Arch Pharmacol 323:328–334CrossRefGoogle Scholar
  31. Su CM, Swamy VC, Triggle DJ (1986) Postsynaptic alpha-adrenoceptor characterization and calcium channel antagonist and activator actions in rat tail arteries from normotensive and hypertensive animals. Can J Physiol 64:909–921CrossRefGoogle Scholar
  32. Van Meel JCA, de Jonge A, Timmermans PBMWM, van Zwieten PA (1981) Selectivity of some alpha adrenoceptor agonists for peripheral alpha-1 and alpha-2 adrenoceptors in the normotensive rat. J Pharmacol Exp Ther 219:760–767PubMedGoogle Scholar
  33. Van Meel JCA, Timmermans PBMWM, Van Zwieten PA (1983) Alpha-1 and alpha-2 adrenoceptor stimulation in the isolated perfused hindquarters of the rat: an in vitro model. J Cardiovasc Pharmacol 5:580–585CrossRefGoogle Scholar
  34. Van Zwieten PA, Timmermans PBMWM, Thoolen MJMC, Wilffert B, de Jonge A (1985) Calcium dependency of vasoconstriction mediated by alpha-1 and alpha-2 adrenoceptors. J Cardiovasc Pharmacol 7:S113-S120CrossRefGoogle Scholar
  35. Weiss RJ, Webb RC, Smith CB (1983) Alpha-2 adrenoceptors on arterial smooth muscle: selective labelling by [3H] clonidine. J Pharmacol Exp Ther 225:599–605PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • J. Atkinson
    • 1
  • N. Trescases
    • 1
  • C. Benedek
    • 2
  • N. Boillat
    • 2
  • A. K. Fouda
    • 1
  • F. Krause
    • 2
  • M. C. Pitton
    • 2
  • C. Rafizadeh
    • 2
  • J. C. de Rivaz
    • 2
  • M. Saute
    • 2
  • M. Sonnay
    • 2
  1. 1.Laboratoire de Pharmacologie, Faculté des Sciences Pharmaceutiques et BiologiquesUniversité de Nancy INancyFrance
  2. 2.Institut de PharmacologieLausanneSwitzerland

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