Inhibition of phosphodiesterase III with milrinone increases renin secretion in human subjects

One of the major signaling molecules involved in the regulation of renin secretion is cyclic AMP (cAMP). The concentration of cAMP in cells is determined in part by the rate of cAMP hydrolysis by several families of phosphodiesterases, especially the phosphodiesterase III family, but little is known about the roles of these enzymes in the control of renin secretion, particularly in humans. The aim of the present study was to investigate the effect of the phosphodiesterase III inhibitor milrinone on renin secretion in human subjects. Milrinone was infused i.v. in eight healthy normotensive subjects in a dose of 100 microgram/kg. Immediately after the infusion, there was a transient increase in systolic pressure from 107 +/- 5 to 116 +/- 5 mm Hg (p <.01), but no significant change in diastolic or mean arterial pressure. Heart rate increased from 67 +/- 2 to 86 +/- 4 beats/min (p <.01) and remained elevated. Plasma renin activity increased in all subjects, the mean value increasing from 3.0 +/- 0.5 to 6.0 +/- 1.1 ng/ml/h at 15 min (p <.01). These results demonstrate that milrinone increases renin secretion in human subjects, thus providing evidence that phosphodiesterase III family participates in the control of renin secretion in humans. The increase in renin secretion does not appear to be mediated by major mechanisms that control renin secretion, and likely results from an increase in cAMP concentration in the juxtaglomerular cells.