L-NAME HYPERTENSION ALTERS ENDOTHELIAL AND SMOOTH-MUSCLE FUNCTION IN RAT AORTA - PREVENTION BY TRANDOLAPRIL AND VERAPAMIL

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-omega-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 approximate to 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.