title: Endothelium-derived relaxing factor and the vascular reply to systemic hypertension.
abstract: Endogenous nitric oxide is an important modulator of vascular smooth muscle tone. The role of nitric oxide in the vascular adaptation to systemic hypertension was examined by using N omega-monomethyl-L-arginine (L-NMMA; 110 micrograms/kg/min), a competitive inhibitor of the conversion of L-arginine to nitric oxide. L-NMMA or saline vehicle (9.6 microL/min) was infused i.v. into several rat models of acute and chronic systemic hypertension. The response to L-NMMA was compared either in uninephrectomized Sprague-Dawley rats treated with deoxycorticosterone on either a high- or low-sodium diet or in untreated uninephrectomized rats on normal chow. Hypertensive deoxycorticosterone rats had a significantly greater pressor response to L-NMMA (139 +/- 2 to 169 +/- 3 mm Hg; N = 9) than did normotensive uninephrectomized rats (112 +/- 4 to 129 +/- 3 mm Hg; N = 7) or deoxycortisterone treated rats on a low-sodium diet (108 +/- 2 to 121 +/- 3 mm Hg; N = 9). By contrast, hypertension induced by the vasoconstrictor angiotensin II did not have an enhanced response (134 +/- 3 to 154 +/- 4 mm Hg; N = 7) nor did spontaneously hypertensive rats (164 +/- 4 to 175 +/- 4 mm Hg; N = 6). This dose of L-NMMA had minimal effects on renal hemodynamics in the normotensive and hypertensive animals, except for those receiving angiotensin II where it led to substantial reductions of inulin and para-aminohippurate clearance. In conclusion, these data point to a role for nitric oxide in the vascular adaptation to volume-mediated hypertension, an effect that was not observed in vasoconstrictor-induced hypertension.
authors.affiliation: Renal Division, Brigham and Women's Hospital, Boston, MA.
authors.forename: A J
authors.initials: AJ
authors.lastname: King
authors.forename: P
authors.initials: P
authors.lastname: Mercer
authors.forename: J L
authors.initials: JL
authors.lastname: Troy
authors.forename: B M
authors.initials: BM
authors.lastname: Brenner
mesh_terms: D000208:Acute Disease; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002908:Chronic Disease; D003900:Desoxycorticosterone / Q000633:toxicity; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D009392:Nephrectomy; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology; D011919:Rats, Inbred Strains / Q000502:physiology; D012079:Renal Circulation / Q000187:drug effects; D012982:Sodium, Dietary / Q000633:toxicity; D014666:Vasomotor System / Q000503:physiopathology*; D019323:omega-N-Methylarginine
chemical_list: D012982:Sodium, Dietary; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D003900:Desoxycorticosterone; D001120:Arginine