Effect of atriopeptin III on renin release in vitro

The ability of atriopeptin III (AP) to directly inhibit renal renin release has not been resolved. This issue was examined in a series of experiments performed in a system of rat renal cortical slices (dry weight 1.91 mg) in which the goal was to explore the effects of Ap on renin release induced by cyclic AMP (cAMP)-coupled stimuli or by agents which are believed to decrease intracellular calcium (Ca_i). Concentration response relationships were initially established for all test agents. The cAMP stimuli utilized were isoproterenol (10^-5M), forskolin (10^-5M), and dibutyryl cAMP (3 × 10^-4M); each of these agents produced a significant increase in renin release in the system (with isoproterenol a 50% increase, with forskolin 37%, and with dibutyryl cAMP 52%). The addition of AP (2.09 × 10^-8,M, a minimum inhibitory concentration derived from preliminary studies) significantly blunted these increases; in the case of the dibutyryl cAMP-stimulated renin release, the inhibition was partial as a significant 25% increase in renin occured in the presence of AP. The addition of the calcium channel blocking agent in diltiazem (10^-4M) resulted in a significant increase in renin release (364 to 567 ng.mg^-1, p<.05) which was not blocked by the addition of AP. Similarly, TMB-8 (0.6 × 10^-4M), another agent thought to lower Ca_i, also resulted in increased renin release (455 to 810 ng.mg^-1), p<.01) which.