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(Hypertension. 1996;27:19-24.)
© 1996 American Heart Association, Inc.

Articles

Nitric Oxide and the Depressor Response to Angiotensin Blockade in Hypertension

Hui Guan; Victoria Cachofeiro; Michael L. Pucci; Pawel M. Kaminski; Michael S. Wolin; Alberto Nasjletti

From the Departments of Pharmacology and Physiology, New York Medical College, Valhalla, NY.

Abstract We investigated the contribution of nitric oxide to the short-term blood pressure reduction caused by interruption of the renin-angiotensin system in angiotensin-dependent hypertension. The blood pressure of rats made hypertensive by coarctation of the aorta between the renal arteries at their origin fell after administration of the angiotensin-converting enzyme inhibitor ramiprilat (2 mg/kg IV; -75±5 mm Hg) or the angiotensin II antagonist losartan (30 mg/kg IV; -79±6 mm Hg). But the antihypertensive effect of these agents was attenuated in rats pretreated with N^G-nitro-L-arginine methyl ester (10 mg/kg IV) to inhibit nitric oxide synthesis (ramiprilat, -23±7 mm Hg; losartan, -37±5 mm Hg). In rats made hypertensive by long-term infusion of angiotensin II (60 ng/min IV, 6 to 7 days), the vasodepressor response to discontinuation of the angiotensin II infusion also was attenuated by pretreatment with the nitric oxide synthesis inhibitor (-52±7 versus -31±7 mm Hg); this attenuation was not demonstrable in rats receiving sodium nitroprusside (1 µg·kg ^-1·min ^-1 IV) to replace the loss of endogenous nitric oxide (-72±9 mm Hg). Pretreatment with N^G-nitro-L-arginine methyl ester did not interfere with the vasodepressor effect of sodium nitroprusside or prazosin in rats with aortic coarctation–induced hypertension or with the blood pressure reduction caused by discontinuation of an infusion of phenylephrine in rats made hypertensive by long-term administration of this drug. These data suggest a contribution of nitric oxide to the blood pressure reduction caused by interruption of the renin-angiotensin system in models of established angiotensin-dependent hypertension.

Key Words: antihypertensive agents • experimental hypertension • losartan • nitric oxide • renin-angiotensin system • angiotensin-converting enzyme inhibitors

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