The effect of prostaglandin synthesis inhibition on the direct stimulation of renin release from rabbit renal cortical slices.
Prostaglandins have been hypothesized to have several mechanistic functions in sympathetically mediated release of renin. The rabbit renal cortical slice system was chosen to examine the prostaglandin dependency of renin release directly stimulated by either a direct adenylate cyclase activator, forskolin, or a beta-agonist, isoproterenol. In this study, we demonstrate that with forskolin (1 X 10(-5) M) or isoproterenol (1 X 10(-6) M), renin release was elevated 2-3 fold above control, and that this increase was shown to accompany a substantial increase in the tissue levels of cAMP (19.5 fold and 3.5 fold respectively). We also demonstrate that the increase in renin release produced by these compounds was not inhibited by cyclooxygenase inhibitors, indomethacin (25 microM) or eicosatetraynoic acid (30 micrograms/ml), nor was it inhibited by the selective prostacyclin synthesis inhibitor, U-51605 (30 micrograms/ml). Each of these inhibitors was demonstrated to block the synthesis of prostaglandins in the cortical slices at the concentrations used. Thus we propose that prostaglandins do not play a role in the induction of renin release resulting from elevated cyclic nucleotide levels or beta-adrenergic stimulation.
D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D005576:Colforsin; D000242:Cyclic AMP / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology*; D007672:Kidney Cortex / Q000378:metabolism*; D008297:Male; D011453:Prostaglandins / Q000096:biosynthesis*; D011463:Prostaglandins H / Q000494:pharmacology; D011817:Rabbits; D012083:Renin / Q000378:metabolism*
D000067956:Adenylyl Cyclase Inhibitors; D004224:Diterpenes; D011453:Prostaglandins; D011463:Prostaglandins H; D005576:Colforsin; C015014:azo analog I; D000242:Cyclic AMP; D012083:Renin; D007545:Isoproterenol; D007213:Indomethacin