The role of renal prostaglandins in the renin response to isoproterenol in the rat in vitro.

Renal prostaglandins (PGs) have been considered to be important mediators of renin release. However, the mechanism and the site of action have not been clarified. To investigate the role of PGs in the control of isoproterenol-induced renin release, we studied the effect of two inhibitors of PG synthesis, indomethacin and meclofenamate, on the renin release stimulated by isoproterenol and dibutyryl cAMP. We used an in vitro superfusion system of rat renal cortical slices. Neither indomethacin nor meclofenamate affected basal renin release. Isoproterenol (8 x 10(-7) M) increased renin and PGE2 release which was blocked by indomethacin (10(-4) M) and meclofenamate (10(-4) M). Dibutyryl cAMP stimulated renin release significantly, and this effect was not blocked by indomethacin (10(-4) M). Moreover, dibutyryl cAMP did not stimulate PGE2 release. In view of the fact that we have previously shown that PG-stimulated renin release is not blocked by propranolol and is enhanced by phosphodiesterase inhibitors, our present experiments suggest that the site of action of PGs on renin release is located between the beta-adrenergic receptor and the generation of cAMP.