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 sm ooth muscle. Here we analyzed the effects on regulation of renal vascu lar function in anesthetized dogs of inhibition of the H+-K+-ATPase by a highly specific inhibitor, NC-1300-B. The compound was injected int ravenously, 15 mg/kg (5.8 x 10(-5) mol wt/kg), into one group of six d ogs, whereas saline was given to a control group of eight. Renal funct ion was measured at controlled levels of renal perfusion pressure rang ing from 110 to 60 mmHg. Renal blood flow (RBF) was higher in the trea ted 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 t han that of the control group. Glomerular filtration rate (GFR) mean v alues of the two groups were not significantly different at any perfus ion pressure level. Renin release was inhibited (P < 0.01) by H+-K+-AT Pase inhibition; at 90 mmHg, the control group mean was 14.3 +/- 4.3 u nits, 4.47 times greater than the treated group mean of 3.2 +/- 1.6 un its. H+-K+-ATPase inhibition with NC-1300-B causes profound renal vaso dilation and inhibition of renin release without affecting regulation of GFR.