Effects of angiotensin converting enzyme inhibitors and of hydralazine on endothelial function in hypertensive rats.
The function of the endothelium is impaired in hypertension. In spontaneously hypertensive rats (SHR), acetylcholine-induced relaxation is decreased and serotonin-induced constriction is increased. The goal of our study was to evaluate the effect of a long-term treatment with cilazapril, a new angiotensin converting enzyme inhibitor, or hydralazine, a vasodilator, on the endothelium-dependent responses in aorta of SHR. Wistar-Kyoto rats were used as normotensive reference. Isolated aortic rings with or without endothelium were suspended in organ chambers. The rings with intact endothelium were contracted with norepinephrine. Acetylcholine-induced relaxation was markedly enhanced by cilazapril treatment. The tension achieved at maximal relaxation was 8 +/- 4% of norepinephrine contraction in the cilazapril-treated SHR versus 55 +/- 5% in the untreated SHR (p less than 0.001). Hydralazine had no significant effect. The effect of serotonin was also markedly modified by cilazapril. In untreated SHR, serotonin induced the release of a vasoconstrictor substance by the endothelium as assessed by the ratio of maximal tension induced by serotonin in rings with endothelium over maximal tension in rings without endothelium, which was greater than 1. This ratio was reversed in cilazapril-treated SHR but not in hydralazine-treated SHR. Captopril had effects similar to cilazapril. Finally, evaluation of carotid arteries showed that cilazapril also prevented morphological changes of the intima in SHR (i.e., infiltration by mononuclear cells). We conclude that angiotensin converting enzyme inhibitors prevent the functional and morphological alterations in endothelium that are found in hypertension and speculate that this action might participate in their antihypertensive effect.
Clozel
M
M
F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Kuhn
H
H
Hefti
F
F
D000109:Acetylcholine / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D017315:Cilazapril; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D006830:Hydralazine / Q000494:pharmacology*; D006973:Hypertension / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012701:Serotonin / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D011724:Pyridazines; D017315:Cilazapril; D006830:Hydralazine; D012701:Serotonin; D002216:Captopril; D000109:Acetylcholine; D007213:Indomethacin