Atherosclerosis and responses of human isolated coronary arteries to endothelium-dependent and -independent vasodilators.
In canine and porcine coronary arteries, experimental atherosclerosis (induced by endothelial denudation followed by a high-cholesterol diet) potentiates the vasoconstrictor effects of histamine, serotonin, and ergonovine. In isolated human atherosclerotic coronary arteries, only hypersensitivity to histamine has been demonstrated. This discrepancy could be due to several factors. First, the atherosclerotic lesions in human vessels are different from those observed in the animal, since experimental atherosclerosis often corresponds only to the early stage of the disease in humans. Second, the human atherosclerotic coronary arteries were isolated mainly from patients with cardiac failure, a condition that alters the responses of coronary smooth muscle to vasoactive amines. With regard to endothelium-dependent vasodilators, marked attenuations of the relaxations to substance P, bradykinin, and the Ca2+ ionophore A23187 have been described in isolated human atherosclerotic arteries. Acetylcholine elicits variable responses in these preparations and even if the arteries are devoid of atherosclerotic lesions, it often fails to relax them. In addition to this endothelial dysfunction, severely atherosclerotic human coronary vessels exhibit a slightly decreased responsiveness to nitroglycerin and SIN-1 but not to forskolin. Another abnormality of the smooth muscle is a marked attenuated beta-adrenergic relaxation. Thus, atherosclerosis of human coronary vessels induces not only marked alterations in endothelium-dependent responses but also modifies the sensitivity to several endothelium-independent vasodilators.
Berkenboom
G
G
Cardiology Department, Erasmus Hospital, Brussels, Belgium.
Unger
P
P
Fontaine
J
J
D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D003324:Coronary Artery Disease / Q000503:physiopathology*; D003331:Coronary Vessels / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D012377:Rodentia; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D005576:Colforsin; C002385:linsidomine; D008981:Molsidomine; D005996:Nitroglycerin; D007545:Isoproterenol