Role of cyclic AMP in the regulation of renin release from the isolated perfused rat kidney

The role of cyclic AMP in the regulation of renin release (RR) was studied in isolated rat kidneys, which were perfused at constant pressure in a single-pass system with a modified Krebs-henseleit solution. Isoproterenol (IP) (2 x 10(-9) to 2 x 10(-6) M) and 3-isobutyl-1-methyl-xanthine (IBMX) (4 x 10(-7) to 7 x 10(-5) M) induced a dose-dependent increase of renal perfusate flow, glomerular filtration rate and urinary sodium excretion. RR was stimulated up to 10-fold above control values within 5 min. At the lowest concentrations IP stimulated RR, but did not affect renal haemodynamics. When IP and IBMX were administered concomitantly, a supraadditive stimulation of RR was observed. Dibutyryl-cAMP (db-cAMP) and 8-Br-cGMP (10(-6) to 10(-4) M) produced a similar dose-dependent vasodilation and natriuresis, but differed in their action on RR. Within 15 min after the start of the infusion, db-cAMP increased RR up to 4-fold, whereas 8-Br-cGMP was without an effect. These results suggest that IP, IBMX and db-cAMP stimulated RR by increasing the concentrations of cAMP in the epitheloid cells and independently of changes in renal haemodynamics and sodium excretion.