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 2a equivalents). Either of two antunflaiunatory 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.

The effect of indomethacin on autoregulation of renal blood flow in the anasthetized dog.

“…Although we had no direct measurement of renal prostaglandin synthesis there is evidence that the doses of indomethacin used here were sufficient to reduce prostaglandin synthesis (Vane, 1971;Ferreira, Moncada & Vane, 1971). Indomethacin, in doses less than those used in the present experiments, has been shown to reduce significantly the efflux of prostaglandins into dog renal venous blood (Aiken Herbaczynska-Cedro & Vane, 1973;Lonigro, Itskovitz, Crowshaw & McGiff, 1973) and to enhance the vasoconstriction caused by angiotensin, which normally promotes prostaglandin release in the absence of indomethacin. Indomethacin abolishes the conversion of labelled arachidonic acid to prostaglandins in homogenates of rabbit kidney (Larsson & Angaard, 1973), and reduces urinary efflux of prostaglandins by 40 %.…”

Urinary prostaglandins. Identification and origin.

“…Studies from this and other laboratories have demonstrated that PG synthesized intrarenally will affect blood flow to the cortex, chiefly that to the juxtamedullary nephrons (29,34). As the synthesis of PG in the kidney occurs almost entirely in the medulla (35), the question arises as to how the PG are transported from medulla to the point of blood flow regulation in the cortex.…”

Uterine prostaglandin E secretion and uterine blood flow in the pregnant rabbit.

“…In previous studies evaluating the renal circulation, Lonigro, Itskovitz, Crowshaw, and McGiff and Kirschenbaum, White, Stein, and Ferris, both noted a decrease in renal blood flow after the administration of meclofenamate or indomethacin (13,14). In addition, in the former study, there was a profound fall in renal venous PGE levels as measured by bioassay techniques.…”