(Hypertension. 1995;26:744.)
© 1995 American Heart Association, Inc.
Articles |
L-NAME Hypertension Alters Endothelial and Smooth Muscle Function in Rat Aorta
Prevention by Trandolapril and Verapamil
From the Division of Cardiology, Cardiovascular Research, University Hospital, Bern (C.F.K., P.M., H.T., T.F.L.), and Department of Research, Laboratory of Vascular Research, University Hospital, Basel (C.F.K., T.F.L.), Switzerland.
Correspondence to Thomas F. Lüscher, MD, Cardiology, University Hospital, Inselspital, CH-3010 Bern, Switzerland.
Abstract Nitric oxide is an important regulator of
vascular function and blood pressure. Chronic administration of nitric
oxide inhibitors provides a new model of hypertension with
pronounced target organ damage. We investigated the effects of oral
treatment with N
-nitro-L-arginine
methyl ester (L-NAME) for 6 weeks on vascular reactivity of the aorta
in Wistar-Kyoto rats. Certain rats received verapamil or
trandolapril in addition to L-NAME. Systolic blood pressure
increased in the L-NAME group (by 
80 mm Hg systolic) but not
in controls or rats treated with verapamil or trandolapril.
Isometric tension changes of aortic rings were recorded.
Endothelium-dependent relaxations to acetylcholine
were reduced in the L-NAME group (58±6% versus 104±1% in placebo,
P<.05) but were normalized by treatment with
verapamil or trandolapril. In contrast,
endothelium-independent relaxations to sodium
nitroprusside were not significantly reduced in L-NAME hypertension but
were slightly enhanced by trandolapril therapy (P<.05).
Acute in vitro incubation of vessels with the thromboxane
receptor antagonist SQ 30741 enhanced the relaxation to
acetylcholine (P<.05) in the L-NAME group only. In
quiescent rings, acetylcholine caused
endothelium-dependent contractions in particular
after in vitro incubation with L-NAME. These contractions tended to be
enhanced in L-NAME hypertension (23±4% versus 14±3% in the placebo
group; P=NS) and were significantly reduced after treatment
with verapamil or trandolapril (P<.05).
Contractions to norepinephrine and angiotensin
I and II were unaffected by L-NAME hypertension, whereas those to
endothelin-1 were reduced (P<.05). Thus, in the aorta,
L-NAME–induced hypertension is associated with impaired
endothelium-dependent relaxations, unmasking the
effects of endothelium-derived vasoconstrictor
prostanoids, and with a specific reduction of the contraction induced
by endothelin-1. Chronic antihypertensive therapy with
verapamil or trandolapril prevented this imbalance of
endothelium-dependent relaxations and contractions
and, in turn, normalized vascular function.
Key Words: endothelins • hypertension • L-NAME • verapamil
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