Nitric oxide and the depressor response to angiotensin blockade in hypertension
Guan, H.; Cachofeiro, V.; Pucci, M.L.; Kaminski, P.M.; Wolin, M.S.; Nasjletti, A.
Hypertension 27(1): 19-24
1996
ISSN/ISBN: 0194-911X PMID: 8591882 Document Number: 455284
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 mu-g cntdot kg-1 cntdot 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.