K-ATP-BLOCKING DIURETIC PNU-37883A REDUCES PLASMA-RENIN ACTIVITY IN DOGS

We determined the effects of the K-adenosine triphosphate (ATP)-blocki ng diuretic PNU-37883A on plasma renin activity (PRA) in conscious and anesthetized dogs. In conscious dogs, oral PNU-37883A (6-60 mg/kg) wa s less potent than hydrochlorothiazide (0.15-1.5 mg/kg) and furosemide (FURO; 0.3-3.0 mg/kg) but exhibited high natriuretic efficacy with li ttle kaliuresis. Unlike the standard diuretics, PNU-37883A reduced PRA by 46-76%, and its high dose minimally affected 24-h urinary aldoster one excretion. PNU-37883A, 1 mg/kg i.v., also blunted the hyperreninem ia induced by 1 mg/kg i.v. FURO. In cannulated dogs, 10 mg/kg i.v. PNU -37883A maximally increased fractional Na+ clearance 140% and reduced PRA 76%, but these effects were accompanied by a mean 13 mm Hg presser effect. In anesthetized dogs, renal artery-infused PNU-37883A(3 mg/kg /h i.r.a.) increased Na+ excretion and reduced renal venous PRA indepe ndent of hemodynamics, whereas half this dosage selectively reduced re nal venous PRA and renin release, independent of hemodynamics and natr iuresis. These data demonstrate that the K-ATP blocker diuretic PNU-37 883A reduces PRA in dogs after oral, i.v., and i.r.a. administration a nd could be a useful pharmacologic agent for exploring the role of K-A TP channels in regulating renin release.