Stimulation of renin secretion by the phosphodiesterase IV inhibitor rolipram

Abstract

It is now generally accepted that the renin secretory response to beta adrenoceptor stimulation is mediated by increased formation of cAMP in the juxtaglomerular cells. It is also known that renin secretion is increased when cAMP metabolism is decreased by phosphodiesterase inhibitors such as theophylline, but it is not known which isoforms of phosphodiesterase are involved. In the present study, we investigated the effect on renin secretion of the phosphodiesterase IV inhibitor rolipram in conscious rabbits. The i.v. administration of rolipram in a dose of 25 microgram/kg followed by infusion at 5 microgram/kg/min in eight rabbits increased mean arterial pressure from 82 +/- 5 to 93 +/- 6 mm Hg (P<.05), decreased HR from 242 +/- 7 to 204 +/- 10 bpm (P<.05) and increased plasma renin activity (PRA) from 6.9 +/- 1.3 to 29.0 +/- 4.2 ng/ml/2 h (P<.01). In a second series of experiments, i.v. infusion of isoproterenol at 0.05 microgram/kg/min increased PRA from 4.1 +/- 0.9 to 9.9 +/- 1.2 ng/ml/2 h (P<.01). Administration of rolipram again increased PRA, and infusion of isoproterenol in the presence of rolipram increased PRA from 30.2 +/- 7.0 to 58.9 +/- 12.6 ng/ml/2 h (P<.01), an increase significantly greater (P<.05) than that produced by isoproterenol alone. Rolipram also prolonged the PRA and HR responses to isoproterenol. These results demonstrate that inhibition of phosphodiesterase IV increases renin secretion and potentiates the renin secretory response to beta adrenoceptor stimulation, thus providing evidence for a role of phosphodiesterase IV in the regulation of renin secretion.