Physiology of Vascular Homeostasis

  • Harsch Sanchorawala
  • John F. KeaneyJr.
Part of the Developments in Cardiovascular Medicine book series (DICM, volume 193)


Over the past 15 years the vasculature has been recognized as more than simply a conduit for the delivery of nutrients and oxygen. The vasculature is an organ composed of endothelial, smooth muscle, and fibroblast cell types with an integrated system of autocrine-paracrine interactions. The vascular system is responsive to changes within both the vascular wall and target organs through the action of local factors that influence its structure and function. In this chapter, we review the anatomic and functional properties of the vasculature, with particular reference to the maintenance of vascular homeostasis.


Nitric Oxide Smooth Muscle Cell Arachidonic Acid Angiotensin Converting Enzyme Vascular Smooth Muscle Cell 
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. 1.
    Gibbons GH, Dzau VJ. The emerging concept of vascular remodeling. N Engl J Med 330:1431, 1994.PubMedCrossRefGoogle Scholar
  2. 2.
    Skinner MP, Raines EW, Ross R. Dynamic expression of alpha 1 beta 1 and alpha 2 beta 1 integrin receptors by human vascular smooth muscle cells. Alpha 2 beta 1 inregrin is required for chemotaxis across type I collagen-coated membranes. Am J Pathol 145:1071, 1994.Google Scholar
  3. 3.
    Young MA, Vatner SF. Regulation of large coronary arteries. Circ Res 59:579, 1985.Google Scholar
  4. 4.
    Vatner S. Regulation of coronary resistance vessels and large coronary arteries. Am J Cardiol 56:16E, 1985.PubMedCrossRefGoogle Scholar
  5. 5.
    Young MA, Knight DR, Vatner SF. Autonomic control of large coronary arteries and resistance vessels. Prog Cardiovasc Dis 30:211, 1987.PubMedCrossRefGoogle Scholar
  6. 6.
    Malik KU. Interaction of arachidonic acid metabliltes and adrenergic nervous system. Am J Med Sci 295:280, 1988.PubMedCrossRefGoogle Scholar
  7. 7.
    Shen W, Ochoa M, Xu X, Wang J, Hintze TH. Role of EDRF/NO in parasympathetic coronary vasodilation following carotid chemoreflex activation in conscious dogs. Am J Physiol 267:H605, 1994.PubMedGoogle Scholar
  8. 8.
    Broten SP, Miyashiro JK, Moncada S, Feigl EO. Role of endothelium-derived relaxing facotr in parasympathetic coronary vasodilation. Am J Physiol 262:H1579, 1992.PubMedGoogle Scholar
  9. 9.
    Vanhoutte PM, Levy MN. Prejunctional cholinergic modulation of adrenergic neurotransmission in the cardiovascular system. Am J Physiol 238:H275, 1990.Google Scholar
  10. 10.
    Ohlstein EH, Berkowitz BA. Vasodilation: Vascular smooth muscle, peptides, autonomic nerves, and endothelium. New York: Raven Press, 1988:113.Google Scholar
  11. 11.
    Scherrer U, Randin D, Vollenweider P, Vollenweider L, Nicod P. Nitrix oxide release accounts for insulin’s vascular effects in humans. J Clin Invest 94:2511, 1994.PubMedGoogle Scholar
  12. 12.
    Creager MA, Liang CS, Coffman JD. Beta adrenergic-mediated vasodilator response to insulin in the human forearm. J Pharmacol Exp Ther 235:709, 1985.PubMedGoogle Scholar
  13. 13.
    Gagnon G, Regoli D, Rioux F. A new bioassay for glucagon. Br J Pharmacol 64:99, 1978.PubMedGoogle Scholar
  14. 14.
    Consentino F, Sill JC, Katusic ZS. Endothelial L-arginine pathway and relaxations to vasopressin in canine basilar artery. Am J Physiol 264:H413, 1993.Google Scholar
  15. 15.
    Vane JR, Anggard EE, Botting RM. Regulatory functions of the vascular endothelium. N Engl J Med 323:27, 1990.PubMedCrossRefGoogle Scholar
  16. 16.
    Schror K. The effect of ptostaglandins and thromboxane A2 on coronary vessel tone — mechanisms of action and therapeutic implications. Eur Heart J l4(Suppl. 1):34, 1993.Google Scholar
  17. 17.
    Francos JA, Eskin SG, McIntire LV, Ives LV. Flow effects on prostacyclin production by cultured human endothelial cells. Science 227:1477, 1985.CrossRefGoogle Scholar
  18. 18.
    Rubanyi GM, Vanhoutte PM. Hypoxia releases a vasoconstrictor substance from the canine vascular endothelium. J Physiol 364:45, 1985.PubMedGoogle Scholar
  19. 19.
    Lincoln TM, Cornwell TL, Taylor AE. cGMP-dependent protein kinase mediates the reduction of Ca+ by cAMP in vascular smooth muscle cells. Am J Physiol 258:C399, 1990.PubMedGoogle Scholar
  20. 20.
    Luscher TF, Vanhoutte PM (eds). The Endothelium: Modulator of Cardiovascular Function, 1st ed. Boca Raton, FL: CRC Press, 1990.Google Scholar
  21. 21.
    Roth DM, Lefer AM. Studies on the mechanism leukotriene induced coronary artery constriction. Prostaglandins 26:573, 1983.PubMedCrossRefGoogle Scholar
  22. 22.
    Tomoike H, Egashira K, Yamada A, Hayashi Y, Nakamura M, Leukotriene C4 and D4-induced diffuse peripheral contstriction of swine coronary artery accompanied by ST elevation on the electrocatdiogram. Circulation 76:480, 1987.PubMedGoogle Scholar
  23. 23.
    Mayatepek E, Hoffman GF. Leukotrienes: Biosynthesis, metabolism, and pathophysiologic significance. Pediatr Res 37:1, 1995.PubMedCrossRefGoogle Scholar
  24. 24.
    Tesfamariam B, Brown ML, Cohen RA. 15-Hydroxyeicosatetraenoic acid and diabetic endothelial dysfunction in rabbit aorta. J Cardiovasc Pharmacol 25:748, 1995.PubMedCrossRefGoogle Scholar
  25. 25.
    Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288:373, 1980.PubMedCrossRefGoogle Scholar
  26. 26.
    Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci USA 84:9265, 1987.PubMedCrossRefGoogle Scholar
  27. 27.
    Stamler JS, Singel DJ, Loscalzo J. Biochemistry of nitric oxide and its redox-activated forms. Science 258:1898, 1992.PubMedCrossRefGoogle Scholar
  28. 28.
    Furchgott R. Role of endothelium in responses of vascular smooth muscle. Circ Res 35:557, 1983.Google Scholar
  29. 29.
    Vita JA, Keaney JF Jr, Loscalzo J. Endothelial dysfunction in vascular disease. In Loscalzo J, Creager MA, Dzau VJ (eds). Vascular Medicine, 2nd ed. Boston: Little Brown, 1996:245.Google Scholar
  30. 30.
    Palmer RM, Ashton DS, Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature 333:664, 1988.PubMedCrossRefGoogle Scholar
  31. 31.
    Sessa WC, Barber CM, Lynch KR. Mutation of N-myristoylation site converts endothelial nitric oxide synthase from a membrane to a cytosolic protein. Circ Res 72:921, 1993.PubMedGoogle Scholar
  32. 32.
    Lopez-Jaramillo P, Gonzalez MC, Palmer RMJ, Moncada S. The crucial role of physiological Ca2+ concentrations in the production of endothelial nitric oxide and the control of vascular tone. Br J Pharmacol 101:489, 1990.PubMedGoogle Scholar
  33. 33.
    Stuehr DJ, Kwon NS, Nathan CF. FAD and GSH participate in macrophage synthesis of nitric oxide. Biochem Biophys Res Commun 168:558, 1990.PubMedCrossRefGoogle Scholar
  34. 34.
    Bolotina VM, Najibi S, Palacino JJ, Pagano PJ, Cohen RA. Nitric oxide directly activates calcium-dependent potassium channels in vascular smooth muscle. Nature 368:850, 1994.PubMedCrossRefGoogle Scholar
  35. 35.
    Cohen RA, Shepherd JT, Vanhoutte PM. The inhibitory role ot the endothelium in the response of isolated coronary arteries to platelets. Science 221:273, 1983.PubMedCrossRefGoogle Scholar
  36. 36.
    Vanhoutte PM. Platelet-derived serotonin, the endothelium, and cardiovascular disease. J Cardiovasc Pharmacol 17(Suppl. 5):S6, 1991.PubMedGoogle Scholar
  37. 37.
    Vanhoutte PM. Hypercholesterolaemia, atherosclerosis and release ot endothelium-derived relaxing factor by aggregating platelets. Eur Heart J 12(Suppl. E):25, 1991.PubMedGoogle Scholar
  38. 38.
    Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332:411, 1988.PubMedCrossRefGoogle Scholar
  39. 39.
    Inoue S, Yunagisawa M, Kimura S, Kasuya Y, Miyauchi T, Goto K, Masaki T. The human endothelin family: Three structurally and pharmacologically distinct isopeptides predicted by three separate genes. Proc Natl Acad Sci USA 86:2863, 1989.PubMedCrossRefGoogle Scholar
  40. 40.
    Resink TJ, Scott-Burden T, Buhler FR. Endothelin stimulates phsospholipase C in cultured vascular smooth muscle cells. Biochem Biophy Res Commun 157:1360, 1988.CrossRefGoogle Scholar
  41. 41.
    Goto K, Kasuya Y, Matsuki N, Takuwa Y, Kurihara H, Ishikawa T, Kimura S, Yanagisawa M, Masaki T. Endothelin activates the dihydropyridine-sensitive, voltage-dependent Ca2+ channel in vascular smooth muscle. Proc Natl Acad Sci USA 86:3915, 1989.PubMedCrossRefGoogle Scholar
  42. 42.
    Boulanger C, Luscher TF. Release of endothelin from the porcine aorta. Inhibition by endothelium-derived nitric oxide. J Clin Invest 85:587, 1990.PubMedGoogle Scholar
  43. 43.
    Falkenhahn M, Golhlke P, Paul M, Stoll M, Unger T. The renin-angiotensin system in the heart and vascular wall: New therapeutic aspects. J Cardiovasc Pharmacol 24(Suppl. 2):S6, 1994.PubMedGoogle Scholar
  44. 44.
    Dzau V. Circulating versus local renin-angiotensin system in cardiovascular homeostasis. Circulation 77(Suppl. 1):4, 1988.Google Scholar
  45. 45.
    Rogerson F, Chai S, Schlawe I, Murray W, Marley PH, Mendelsohn F. Presence of angiotensin converting enzyme in the adventitia of large blood vessels. J Hypertens 10:615, 1992.PubMedCrossRefGoogle Scholar
  46. 46.
    Ullian MF, Linas SL. Angiotensin II surgace receptor coupling to inositol triphosphate formation in vascular smooth muscle cells. J Biol Chem 265:195, 1990.PubMedGoogle Scholar
  47. 47.
    Szabo B, Hedler L, Schurr C, Starke K. Periperal pre-synaptic facilitatory effect of angiotensin II on noradrenaline release in anesthetized rabbits. J Cardiovasc Pharmacol 15:968, 1990.PubMedCrossRefGoogle Scholar
  48. 48.
    Vanhoutte PM, Boulanger CM, Illiano SC, Nagao T, Vidal M, Mombouli JV. Endothelium-dependent effects of converting-enzyme inhibitors. J Cardiovasc Pharmacol 22(Suppl. 5):S10, 1993.Google Scholar
  49. 49.
    Marthel W, Markwardt F. Aggregation of blood platelets by adrenaline and its uptake. Biochem Pharmacol 24:1903, 1975.CrossRefGoogle Scholar
  50. 50.
    Folts JD. An in vivo model of experimental arterial stenosis, intimal damage, and periodic thrombosis. Circulation 83(Suppl. IV):IV3, 1991.PubMedGoogle Scholar
  51. 51.
    Muller JK, Tofler GH, Verrier RL. Sympathetic activity as the cause of the morning increase incardiac events. A likely culprit, but the evidence remains controversial. Circulation 91:2508, 1995.PubMedGoogle Scholar
  52. 52.
    Yao S-K, Ober JC, Krishnaswami A, Ferguson JJ, Anderson HV, Golino P, Buja LM, Willerson JT. Endogenous nitric oxide protects against platelet aggregation and cyclic flow variations in stenosed and endothelium-injured arteries. Circulation 86:1302, 1992.PubMedGoogle Scholar
  53. 53.
    Booyse FM, Marr J, Yang DC, Guiliani D, Rafelson ME Jr. Mechanism of cyclic adenosine 3’,5’-monophosphate regulation of platelet membrane phosphorylation-dephosphorylation, Ca binding, and aggregation. In Lutin ON (ed). Platelets. Amsterdam: Exerpta Medica, 1975:84.Google Scholar
  54. 54.
    Chevy F, Wolf C, Colard O. A unique pool of free arachidonate serves as substrate for both cyclooxygenase and lipoxygenase in platelets. Lipids 26:1080, 1991.PubMedCrossRefGoogle Scholar
  55. 55.
    Hill TD, Thite JG, Rao GH. Platelet hypersinsitivity induced by l-chloro-2, 4-dinitrobenzene, hydroperoxides, and inhibition of lipoxygenase. Thromb Res 53:447, 1989.PubMedCrossRefGoogle Scholar
  56. 56.
    Freedman JE, Frei B, Welch GN, Loscalzo J. Glutathrove peroxidase potentiates the inhibition of platelet function by 5-nitrosothiols. J Clin Invest 96:394, 1995.PubMedGoogle Scholar
  57. 57.
    Malinski T, Radomski MW, Taha Z, Moncada S. Direct electrochemical measurement of nitric oxide released from human platelets. Biochem Biophys Res Commun 194:960, 1993.PubMedCrossRefGoogle Scholar
  58. 58.
    Azuma H, Ishikawa M, Sekizaki S. Endothelium-dependent inhibition of platelet aggregation. Br J Pharmacol 88:411, 1986.PubMedGoogle Scholar
  59. 59.
    Radomski MW, Palmer RMJ, Moncada S. The role of nitric oxide and cGMP in platelet adhesion to the vascular endothelium. Biochem Biophys Res Commun 148:1482, 1987.PubMedCrossRefGoogle Scholar
  60. 60.
    Mendelsohn ME, O’Neill S, George D, Loscalzo J. Inhibition of fibrinogen binding to human platelets by S-nitroso-N-acetylcysteine. J Biol Chem 265:19028, 1990.PubMedGoogle Scholar
  61. 61.
    Ludmer PL, Selwyn AP, Shook TL, Wayne RR, Mudge GH, Alexander RW, Ganz P. Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Engl J Med 315:1046, 1986.PubMedCrossRefGoogle Scholar
  62. 62.
    Mizuno K, Satomura K, Miyamoto A, Arakawa K, Shibuya T, Arai T, Kurita A, Nakamura H, Ambrose JA. Angioscopic evaluation of coronary-artery thrombi in acute coronary syndromes. N Engl J Med 326:287, 1992.PubMedCrossRefGoogle Scholar
  63. 63.
    DeWood MA, Spores J, Notske R, Mouser LT, Burroughs R, Golden MS, Lang HT. Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction. N Engl J Med 303:897, 1980.PubMedCrossRefGoogle Scholar
  64. 64.
    Keaney JF Jr, Loscalzo J. The pharmacology of thrombolytic agents. In Loscalzo J, Schaefer AI (eds). Thrombosis and Hemorrhage. Boston: Blackwell Scientific, 1173, 1991.Google Scholar
  65. 65.
    Loskutoff DJ, Edgington DS. Synthesis of a fibrinolytic activator and inhibitor by endothelial cells. Proc Natl Acad Sci USA 74:3903, 1977.PubMedCrossRefGoogle Scholar
  66. 66.
    Levin EG, Marzec U, Anderson J, Harker LA. Thrombin stimulates tissue plasminogen activator release from cultured human endothelial cells. J Clin Invest 74:1988, 1984.PubMedGoogle Scholar
  67. 67.
    Hanss M, Collen D. Secretion of tissue-type plasminogen activator and plasminogen activator inhibitor by cultured human endothelial cells: Modulation by thrombin, endotoxin and histamine. J Lab Clin Med 109:97, 1987.PubMedGoogle Scholar
  68. 68.
    Hekman CM, Loskutoff DJ. Fibrinolytic pathways and the endothelium. Semin Thromb Haemost 13:514, 1987.CrossRefGoogle Scholar
  69. 69.
    Gelehrter TD, Szneyeer-Laszuk R. Thrombin induction of plasminogen activator inhibitor in cultured human endothelial cells. J Clin Invest 77:165, 1986.PubMedGoogle Scholar
  70. 70.
    Vaughan DE, Lazos SA, Tong K. Angiotensin II regulates the expression of plasminogen activator inhibitor-1 in cultured endothelial cells. A potential link between the renin angiorensin system and thrombosis. J Clin Invest 95:995, 1995.PubMedCrossRefGoogle Scholar
  71. 71.
    Aznar J, Estelles A, Tormo G, Sapena P, Tormo V, Blanch S, Espana F. Plasminogen activator inhibitor activity and other fibrinolytic variables in patients with coronary artery disease. Br Heart J 59:535, 1988.PubMedCrossRefGoogle Scholar
  72. 72.
    Paramo JA, Colucci M, Collen D, van de Werf F. Plasminogen activator inhibitor in the blood of patients with coronary artery disease. Br Med J 291:573, 1985.Google Scholar
  73. 73.
    Auwerx J, Bouillon R, Collen D, Gaboers J. Tissue-type plasminogen activator antigen and plasminogen activator inhibitor in diabetes mellitus. Arteriosclerosis 8:68, 1988.PubMedGoogle Scholar
  74. 74.
    Pfeffer MA, Braunwald E, Moye LA, Basra L, Brown EJ Jr, Cuddy TE, Davis BR, Geltman EM, Goldman S, Flaker GC, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 327:676, 1992.CrossRefGoogle Scholar
  75. 75.
    Alderman MH, Madhavan S, Ooi WL, Cohen H, Sealey JE, Laragh JH. Association of the renin-sodium profile with the risk of myocardial infarction in patients with hypertension. N Engl J Med 324:1098, 1991.PubMedCrossRefGoogle Scholar
  76. 76.
    Ridker PM, Gaboury CL, Conlin PR, Seely EW, Williams GH, Vaughan DE. Stimulation of plasminogen activator inhibitor in vivo by infusion of angiotensin II. Evidence of a potential interaction between the renin-angiotensin system and fibrinolytic function. Circulation 87:1969, 1993.PubMedGoogle Scholar
  77. 77.
    Horvat R, Palade GE. Thrombomodulin and thrombin localization on the vascular endothelium; their internalization and transcytosis by plasmalemmal vesicles. Eur J Cell Biol 61:299, 1993.PubMedGoogle Scholar
  78. 78.
    Esmon CT. The roles of protein C and thrombomodulin in the regulation of blood coagulation. J Biol Chem 264:4743, 1989.PubMedGoogle Scholar
  79. 79.
    Stern DM, Nawroth PP, Harris K, Esmon CT. Cultured bovine aortic endothelial cells promote activated protein C-protein S-mediated inactivation of factor Va. J Biol Chem 261:713, 1986.PubMedGoogle Scholar
  80. 80.
    Marlar RA, Kleiss AJ, Griffin JH. Mechanism of activation of human activated protein C, a thrombindependent anticoagulant enzyme. Blood 59:1067, 1982.PubMedGoogle Scholar
  81. 81.
    De Fouw NJ, van Hinsbergh VW, de Jong YF, Haverkate F, Bertina RM. The interaction of activated prorein C and thrombin with the plasminogen activator inhibitor released from human endothelial cells. Thromb Haemost 57:176, 1987.PubMedGoogle Scholar
  82. 82.
    Marcum JA, Mckinney JB, Rosenberg RD. Acceleration of thrombin-antithrombin complex formation in rat hindquarters via hepannlike molecules bound to the endothelium. J Clin Invest 74:341, 1984.PubMedGoogle Scholar
  83. 83.
    Tollefsen DM, Petska CA, Nibafi WJ. Activation of heparin cofactor II by dermatan sulfate. J Biol Chem 258:6713, 1983.PubMedGoogle Scholar
  84. 84.
    Jaffe EA, Hoyer LW, Nachman RL. Synthesis of von Williebrand facror by cultured human endothelial cells. Proc Natl Acad Sci USA 71:1906, 1974.PubMedCrossRefGoogle Scholar
  85. 85.
    Reuning U, Bang NU. Regulation of the urokinase-type plasminogen activator receptor on vascular smooth muscle cells is under the control of thrombin and other mitogens. Arterioscler Thromb 12:1161, 1992.PubMedGoogle Scholar
  86. 86.
    Marks DS, Vita JA, Folts JD, Keaney JF Jr, Welch GN, Loscalzo J. Inhitition of neointimal proliferation in rabbits after vascular injury by a single treatment with a protein adduct of nitric oxide. J Clin Invest 95:2630, 1995.Google Scholar
  87. 87.
    O’Rourke ST, Vanhoutte PM. Vascular pharmacology. In Loscalzo J, Creager MA, Dzao VJ (eds). Vascular Medicine, 1st ed. Boston: Little Brown, 1992:133.Google Scholar

Copyright information

© Kluwer Academic Publishers 1997

Authors and Affiliations

  • Harsch Sanchorawala
  • John F. KeaneyJr.

There are no affiliations available

Personalised recommendations