Reduction in renin release and renal vascular resistance by H(+)-K(+)-ATPase inhibition.
Results from previous experiments in our laboratory suggested that a H(+)-K(+)-adenosinetriphosphatase (H(+)-K(+)-ATPase) was present in vascular smooth muscle. Here we analyzed the effects on regulation of renal vascular function in anesthetized dogs of inhibition of the H(+)-K(+)-ATPase by a highly specific inhibitor, NC-1300-B. The compound was injected intravenously, 15 mg/kg (5.8 x 10(-5) mol wt/kg), into one group of six dogs, whereas saline was given to a control group of eight. Renal function was measured at controlled levels of renal perfusion pressure ranging from 110 to 60 mmHg. Renal blood flow (RBF) was higher in the treated group at all levels of perfusion pressure; at 70 mmHg, the treated group RBF was 5.85 +/- 1.00 ml.min-1.g kidney wt-1, 71% greater than that of the control group. Glomerular filtration rate (GFR) mean values of the two groups were not significantly different at any perfusion pressure level. Renin release was inhibited (P < 0.01) by H(+)-K(+)-ATPase inhibition; at 90 mmHg, the control group mean was 14.3 +/- 4.3 units, 4.47 times greater than the treated group mean of 3.2 +/- 1.6 units. H(+)-K(+)-ATPase inhibition with NC-1300-B causes profound renal vasodilation and inhibition of renin release without affecting regulation of GFR.
Lin
H
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Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson 39216-4505, USA.
Young
D B
DB
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010477:Perfusion; D011188:Potassium / Q000097:blood; D054328:Proton Pump Inhibitors; D012079:Renal Circulation / Q000187:drug effects*; D012083:Renin / Q000378:metabolism*; D012964:Sodium / Q000097:blood; D014655:Vascular Resistance / Q000187:drug effects
D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D054328:Proton Pump Inhibitors; C057696:NC 1300 B; D012964:Sodium; D012083:Renin; D011188:Potassium