Renal prostaglandins E2 and I2. Aspects of metabolism, and relationship to renal hemodynamics and renin release mechanisms.

Similar distributions of prostaglandins in urine and renal venous blood both during prostaglandin infusion and stimulated synthesis indicated a vascular origin for both urinary and renal venous PGE2 and PGI2. Various stimulation procedures demonstrated that the renal vasculature releases PGE2 and PGI2 in a fixed proportion. Renal degradation of circulating prostaglandins was not influenced by ureteral occlusion and seems to be mainly confined to the blood vessels. The vascular capacity for both synthesis and degradation was much greater for PGE2 than for PGI2. Urinary PGE2 was shown to be of renal origin, but constituted a small and variable fraction of renally produced PGE2, making it a poor estimate of renal PGE2 synthesis. Urinary 6-keto-PGF1 alpha may originate from renal PGI2 production or from circulating 6-keto-PGF1 alpha which readily appears in the urine. Equimolar infusions of PGE2 and PGI2 demonstrated that PGI2 was a more potent stimulator of renin release than PGE2, but the difference seemed to be mainly due to differences in degradation and not to differences in intrinsic potency. Prostaglandins stimulated renin release only when the intrarenal mechanisms for renin release were activated and not at control blood pressure and free urine flow. beta-adrenoceptor agonists stimulated renin release independently of activation of the macula densa, but required activation of the hemodynamic mechanism. Ethacrynic acid activated both the hemodynamic and the macula densa mechanism, but had no direct stimulatory effect on renin release. PGE2 and PGI2 were released during autoregulatory vasodilation, but neither PGE2 nor PGI2 participated in the autoregulatory mechanism. Autoregulatory and prostaglandin mediated vasodilation seems to be independent. Descending autoregulatory vasodilation was demonstrated during successive reductions in RAP, but a more simultaneous dilation of all preglomerular vessels was indicated during successive elevations of ureteral pressure. This difference may be due to participation of TGF together with the myogenic mechanism in autoregulation of RBF. Participation of TGF may also explain why prostaglandin and renin release dissociate during successive reductions in RAP, but increase in parallel during successive elevations of ureteral pressure. It also explains why maximal renin release induced both by the hemodynamic and the macula densa mechanism coincides with the breaking point of the RBF autoregulatory curve, and why loop diuretics induce complete autoregulatory vasodilation at control blood pressure.