Endothelium, arachidonic acid, and coronary vascular tone.
Vasoactive mediators play an important role in the control of coronary vascular tone. Arachidonic acid (AA) metabolites and endothelium-derived vasoactive factors have been implicated in coronary vasoregulation. AA can be metabolized via three separate routes in blood vessels, mediated by cyclooxygenase, lipoxygenase, and cytochrome P-450-dependent monooxygenase enzymes. AA can evoke endothelium-dependent relaxations that are due in part to the formation of cytochrome P-450-dependent metabolites, inasmuch as drugs that modify cytochrome P-450 activity produce parallel changes in endothelium-dependent relaxations to AA. Moreover, some cytochrome P-450-derived metabolites formed biologically cause relaxations of isolated blood vessels. A cytochrome P-450-dependent pathway does not appear to contribute to endothelium-dependent relaxations induced by acetylcholine, which suggests that there may be a number of endothelium-derived relaxing factors (EDRFs). In addition, two endothelium-derived contractile factors have been described, including an unidentified cyclooxygenase metabolite of AA and a polypeptide isolated from cultured cells. As both prostaglandin I2 and acetylcholine-induced EDRF also inhibit platelet aggregation, endothelial injury and loss of these factors may predispose to vasospasm precipitated by release of platelet-derived mediators such as thromboxane A2 (TXA2) and 5-hydroxytryptamine. Unstable angina may be a clinical syndrome in which these events occur, which can be alleviated by inhibition of platelet activation and TXA2 formation with aspirin. Attenuation of endothelium-dependent relaxations can also occur without loss of endothelial cells. Neutrophil-endothelium interactions, precipitated by an ischemic episode, may initiate endothelial dysfunction and underlie the development of vasospasm in some conditions. Whether increased production of endothelium-derived contractile factors also occurs in vasospastic conditions remains to be determined.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D003326:Coronary Circulation; D003329:Coronary Vasospasm / Q000503:physiopathology; D003331:Coronary Vessels / Q000378:metabolism* / Q000503:physiopathology; D004285:Dogs; D004727:Endothelium / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis / Q000502:physiology; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology; D009504:Neutrophils / Q000502:physiology; D011453:Prostaglandins / Q000096:biosynthesis / Q000502:physiology; D014666:Vasomotor System / Q000503:physiopathology*
D001095:Arachidonic Acids; D011453:Prostaglandins; D016718:Arachidonic Acid; D011464:Epoprostenol