Effects of perindoprilat on endothelium-dependent relaxations and contractions in isolated blood vessels.
Experiments were designed to study the effects of perindoprilat (S 9780) on endothelium-dependent and -independent relaxations and contractions in isolated blood vessels. Rings of either canine femoral, basilar or left anterior descending coronary arteries, pulmonary veins, or thoracic aortas from normotensive and hypertensive rats were suspended in organ chambers for isometric tension measurement. Perindoprilat did not evoke endothelium-dependent or -independent relaxations of femoral arteries, basilar arteries, coronary arteries, or rat aortas. The compound did not affect the endothelium-independent relaxations induced by isoproterenol and nitroglycerin in canine femoral arteries. However, when given to rings of canine basilar and coronary arteries, increasing concentrations of perindoprilat potentiated the endothelium-dependent relaxation to bradykinin. In addition, the drug potentiated the endothelium-dependent relaxations to acetylcholine and thrombin in preparations of canine left anterior descending coronary arteries. In contrast, perindoprilat did not cause changes in tension when given in the presence of either adenosine diphosphate, serotonin, or arginine-vasopressin. The compound did not modify the endothelium-dependent contractions evoked by the calcium ionophore A23187 and acetylcholine in canine basilar arteries. It also did not alter endothelium-dependent contractions to arachidonic acid or to hypoxia in canine pulmonary veins or to acetylcholine in the aorta of the spontaneously hypertensive rat.(ABSTRACT TRUNCATED AT 250 WORDS)
Kerth
P A
PA
Department of Medicine, Baylor College of Medicine, Houston, TX 77030.
Vanhoutte
P M
PM
D000109:Acetylcholine / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013917:Thrombin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; C053500:perindoprilat; D013917:Thrombin; D000109:Acetylcholine; D001920:Bradykinin