title: Nitric oxide and the depressor response to angiotensin blockade in hypertension.
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 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.
authors.affiliation: Department of Pharmacology, New York Medical College, Valhalla 10595, USA.
authors.forename: H
authors.initials: H
authors.lastname: Guan
authors.forename: V
authors.initials: V
authors.lastname: Cachofeiro
authors.forename: M L
authors.initials: ML
authors.lastname: Pucci
authors.forename: P M
authors.initials: PM
authors.lastname: Kaminski
authors.forename: M S
authors.initials: MS
authors.lastname: Wolin
authors.forename: A
authors.initials: A
authors.lastname: Nasjletti
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001017:Aortic Coarctation / Q000150:complications; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D006973:Hypertension / Q000139:chemically induced / Q000209:etiology / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D017257:Ramipril / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood; D013777:Tetrazoles / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D009569:Nitric Oxide; C052549:ramiprilat; D001120:Arginine; D019001:Nitric Oxide Synthase; D012083:Renin; D019808:Losartan; D017257:Ramipril; D019331:NG-Nitroarginine Methyl Ester