Endothelium-derived relaxing factor and the vascular reply to systemic hypertension.
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.
King
A J
AJ
Renal Division, Brigham and Women's Hospital, Boston, MA.
Mercer
P
P
Troy
J L
JL
Brenner
B M
BM
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
D012982:Sodium, Dietary; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D003900:Desoxycorticosterone; D001120:Arginine