Peptide-induced prostaglandin biosynthesis in the renal-vein-constricted kidney.

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The ipsilateral kidney was removed from a rabbit 48h after unilateral partial renal-vein-constriction and was perfused with Krebs-Henseleit media at 37 degrees C. Hourly administration of a fixed dose of bradykinin to the renal-vein-constricted kidney demonstrated a marked time-dependent increase in the release of bioassayable prostaglandin E(2) and thromboxane A(2) into the venous effluent as compared with the response of the contralateral control kidney. The renal-vein-constricted kidney produced up to 60 times more prostaglandin E(2) in response to bradykinin after 6h of perfusion as compared with the contralateral kidney; thromboxane A(2) was not demonstratable in the contralateral kidney. Inhibition of protein synthesis de novo in the perfused renal-vein-constricted kidney with cycloheximide lessened the hormone-stimulated increase in prostaglandin E(2) by 94% and in thromboxane A(2) by 90% at 6h of perfusion. Covalent acetylation of the renal cyclo-oxygenase by prior oral administration of aspirin to the rabbit inhibited initial bradykinin-stimulated prostaglandin E(2) biosynthesis 71% at 1h of perfusion. However, there was total recovery from aspirin in the renal-vein-constricted kidney by 2h of perfusion after bradykinin stimulation. Total cyclo-oxygenase activity as measured by [(14)C]arachidonate metabolism to labelled prostaglandins by renal cortical and renal medullary microsomal fractions prepared from 6h-perfused kidneys demonstrated that renal-vein-constricted kidney-cortical cyclo-oxygenase activity was significantly greater than the contralateral-kidney-cortical conversion, whereas medullary arachidonate metabolism was comparable in both the renal-vein-constricted kidney and contralateral kidney. These data suggest that perfusion of a renal-vein-constricted kidney initiates a time-dependent induction of synthesis of prostaglandin-producing enzymes, which appear to be primarily localized in the renal cortex. The presence of the synthetic capacity to generate very potent vasodilator and vasoconstrictor prostaglandins in the renal cortex suggests that these substances could mediate or modulate changes in renal vascular resistance in pathological states.