ramiprilat and Aortic-Coarctation

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 NG-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 microgram.kg-1.min-1 IV) to replace the loss of endogenous nitric oxide (-72 +/- 9 mm Hg). Pretreatment with NG-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.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Aortic Coarctation; Arginine; Biphenyl Compounds; Blood Pressure; Hypertension; Imidazoles; Losartan; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Ramipril; Rats; Rats, Sprague-Dawley; Renin; Tetrazoles; Vasoconstrictor Agents