Role of NO on pressure-natriuresis in Wistar-Kyoto and spontaneously hypertensive rats.
We investigated the role of the endothelium-derived relaxing factor nitric oxide (NO) on pressure-natriuresis in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) using in vivo perfusion studies. Differences in the neural and hormonal background to the kidney were minimized by renal denervation and by holding plasma vasopressin, aldosterone, corticosterone, and norepinephrine levels constant by intravenous infusion. In WKY, elevation of renal perfusion pressure (RPP) from 115 to 157 mm Hg increased urinary sodium excretion 4.5 to 14.8 microEq/min/g kidney wt, and the slope of its linear regression was 0.21 microEq/min/g kidney wt/mm Hg. Infusion of an inhibitor of NO synthase, L-NMMA (1 mg/min/kg), lowered this slope (P < 0.05) but L-arginine (3 mg/min/kg) did not change it. By contrast, the impaired pressure-natriuresis response of SHR was ameliorated by L-arginine (slope: 0.08 to 0.16; P < 0.05), while L-NMMA did not blunt it further. GFR and renal plasma flow (RPF) were well autoregulated in both strains, but L-NMMA lowered RPF significantly (SHR: from 4.2 to 2.6 ml/min/g kidney wt; WKY: 4.5 to 2.5 ml/min/g kidney wt). Moreover, when infused simultaneously, all these individual effects of L-NMMA and L-arginine were nullified. These results suggest that NO plays an important role in the pressure-natriuresis mechanism.
Ikenaga
H
H
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Suzuki
H
H
Ishii
N
N
Itoh
H
H
Saruta
T
T
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology; D008297:Male; D009318:Natriuresis / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases