(Hypertension. 1996;27:25-31.)
© 1996 American Heart Association, Inc.
Articles |
Antihypertensive Therapy Prevents Endothelial Dysfunction in Chronic Nitric Oxide Deficiency
Effect of Verapamil and Trandolapril
From Cardiology and Cardiovascular Research, University Hospital, Bern, Switzerland.
Correspondence to Thomas F. Lüscher, MD, Professor of Medicine, Cardiology, University Hospital, Inselspital, CH-3010 Bern, Switzerland.
Abstract The objective of this study was to examine the
effects of long-term antihypertensive therapy on blood pressure and
vascular responses of resistance arteries during prolonged inhibition
of nitric oxide synthesis. Four groups of 6-week-old Wistar-Kyoto
rats were treated with either placebo as controls or
N
-nitro-L-arginine methyl ester
(L-NAME) alone or in combination with verapamil or with
trandolapril. Drugs were given orally for 6 weeks or short-term in
vitro to vessels obtained from untreated rats.
Endothelium-dependent and -independent relaxations
as well as contractions were studied in isolated perfused mesenteric
and renal arteries with an arteriograph. Kidney nitric oxide synthase
activity was also evaluated. Verapamil and trandolapril
prevented the increase in systolic blood pressure and the
blunted acetylcholine-induced relaxations that occurred with L-NAME
treatment without improving the nitric oxide synthase activity. Both
antihypertensive regimens also normalized sensitivity to sodium
nitroprusside, which was enhanced by L-NAME. In contrast,
short-term in vitro preincubation with verapamil or
trandolaprilat in the presence of L-NAME did not improve the impaired
relaxations to acetylcholine. Long-term but not short-term
therapy with a calcium antagonist or
angiotensin-converting enzyme inhibitor
improved the blunted endothelium-dependent
relaxations in nitric oxide–deficient hypertension. These findings
strongly suggest that the role of other vasodilator systems, which
normally do not regulate vascular tone, is enhanced with long-term
but not short-term treatment with these drugs. These observations
emphasize the potential importance of these treatments in the
management of hypertension in which nitric oxide production is
diminished.
Key Words: L-NAME • nitric oxide • antihypertensive therapy • endothelium-derived relaxing factors
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