Angiotensin (A I, A II, A III) receptor characterization. Correlation of prostaglandin release with peptide degradation.

We examined the ability of the angiotensins (A I, A II, A III) to release a prostaglandin E (PGE)-like substance in the isolated Krebs' perfused kidney and mesenteric vasculature of the rabbit by parallel bioassay. In the kidney, the order of potency for PGE release was A II greater than A III greater than A I with ED50's of 36, 100, and 500 pmol, respectively. In the mesenteric preparation, on the other hand, the order of potency was A III greater than A II greater than A I with ED50's of 75, 125, and 500 pmol, respectively. During one transit through the kidney 72-76% of bioassayable A I and A II was degraded. A III was 89% metabolized. In contrast, the mesenteric vasculature inactivated only 27% of A II and 23% of A III. This data suggests an inverse relationship between renal peptide degradation and PGE release. For characterization of the renal angiotensin receptor-mediating PGE release, dissociation constants (KB) of the competitive angiotensin antagonists [IIe7]-A III and [Sar1, IIe3]-A II were determined with each angiotensin. KB values of the individual antaganists were not significantly different with A I, A II, or A III; this finding suggests that one renal angiotensin receptor is involved with PGE release.