Dependency of Renal Blood Flow on Prostaglandin Synthesis in the Dog

Abstract

Inhibition of prostaglandin synthesis in chloralose-anesthetized dogs reduced renal blood flow, and this reduction closely correlated (r=0.92, P <0.01) with a decline in the renal efflux of a substance having the properties of PGE 2 . We used solvent extraction and thin-layer chromatography coupled with parallel bioassay to identify and assay the PGE- and PGF-like substances (expressed as PGE 2 and PGF 2α equivalents). Either of two antiinflammatory acids, indomethacin or meclofenamate, that inhibited conversion of 14 C-arachidonic acid to prostaglandins in renal homogenates decreased the basal concentration of a PGE-like substance in renal venous blood to 0.06 ± 0.02 ng/ml from a mean control value of 0.34 ± 0.10 ng/ml ( P <0.01). This change was associated with a mean reduction in renal blood flow of 45% in spite of increased renal perfusion pressure. Femoral blood flow and cardiac output were variably and insignificantly affected. Changes in the renal efflux of a PGF-like substance induced by indomethacin were unrelated to the decline in renal blood flow. Changes in the efflux of a PGE-like substance from the femoral vascular bed were unrelated to the small and variable changes in femoral blood flow. Extrarenal factors, i.e., humoral, nervous, or cardiopulmonary factors, did not account for the decline in renal blood flow produced by the inhibitors of prostaglandin synthesis, since the inhibitors produced identical effects in the isolated blood-perfused canine kidney. We concluded that PGE 2 participates in maintaining renal vascular tone which heretofore has been ascribed to autonomous, intrinsic renal arteriolar activity.