Inhibition of prostaglandin synthesis by indomethacin augments the renal vasodilator response to bradykinin in the anesthetized dog.
It has been proposed that the increase in renal blood flow (RBF) produced by bradykinin (BK) is mediated or amplified by the intrarenal generation of prostaglandins. The present investigation was designed to explore these relationships further. In anesthetized dogs, the renal arterial infusion of BK (100 ng/kg per min), prior to the intravenous administration of indomethacin, produced a 93 +/- 14% increase in RBF and an increase in the renal venous concentration of a prostaglandin E-like substance ("PGE") from 51 +/- 23 to 235 +/- 73 pg/ml as determined by bioassay. Following indomethacin (5 mg/kg), the same dose of BK produced a 151 +/- 18% increase in RBF (P less than 0.001 compared to the preindomethacin increase) and the concentration of "PGE" remained largely below the threshold of sensitivity of the bioassay system. In three experiments, a highly sensitive and specific radioimmunoassay technique was used to obtain better quantitative estimates of concentrations of E2-like ("PGE2") and F2alpha-like ("PGF2alpha") substances so that determinations of renal efflux could be made. Thus, prior to indomethacin, BK administration increased RBF by 142 +/- 39 ml/min and was associated with a 26-fold increase in renal efflux of "PGE2" and a 12-fold increase in "PGF2alpha." After indomethacin, the effluxes of both "PGE2" and "PGF2alpha" decreased to negligible levels and were not influenced by BK infusion, although RBF increased by 225 +/- 75 ml/min. These results are not compatible with the hypothesis that intrarenal prostaglandins mediate or amplify the renal vasodilator response to BK.
D000818:Animals; D001920:Bradykinin / Q000008:administration & dosage / Q000494:pharmacology*; D004285:Dogs; D007213:Indomethacin / Q000494:pharmacology*; D007261:Infusions, Intra-Arterial; D007668:Kidney / Q000098:blood supply / Q000378:metabolism*; D007679:Kidney Medulla / Q000378:metabolism; D011458:Prostaglandins E / Q000096:biosynthesis*; D011460:Prostaglandins F / Q000096:biosynthesis*; D011863:Radioimmunoassay; D014664:Vasodilation / Q000187:drug effects*
D011458:Prostaglandins E; D011460:Prostaglandins F; D001920:Bradykinin; D007213:Indomethacin