Hypertension, Vol 16, 532-540, Copyright © 1990 by American Heart Association
M Clozel, H Kuhn and F Hefti
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.
ARTICLES
Effects of angiotensin converting enzyme inhibitors and of hydralazine on endothelial function in hypertensive rats
F. Hoffmann-La Roche Ltd, Basel, Switzerland.
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