Stimulation of microsomal prostaglandin synthesis by a blood plasma constituent which augments autoregulation and maintenance of vascular tone in isolated rabbit hearts
Infusion of small amounts of plasma (1-2%) into isolated hearts perfused with Tyrode's solution causes vasoconstriction and augments regulation of coronary flow in response to changes in perfusion pressure (autoregulation). When plasma infusion is stopped, the vasoconstrictor effect dissipates within 5 minutes, whereas the autoregnlatory response remains for about 15 minutes. Thus the plasma-augmented autoregubtory response is not dependent on plasma-Induced vasoconstriction. Indomethadn (10
... /ml), an inhibitor of prostaglandin synthetase, causes coronary vasodflation and also abolishes the lingering autoregulatory response. These effects of indomethacin are counteracted by the addition of 1.5% plasma to the perfusate. Purification procedures led to the extraction of an active material from plasma which migrates as a single substance in thin layer chromatograms. This substance causes coronary vasoconstriction, augments autoregulation, and counteracts the effects of indometbacin in isolated rabbit hearts as effectively as plasma. The purified vasoactive substance stimulates a 2-fold increase in cardiac microsomal prostaglandin synthesis and a 5-fold increase using renal microsomal preparations. This substance counteracts indomethadn-induced inhibition of prostaglandin synthesis in microsomal preparations. These results provide convincing evidence that the effects of this pbtma constituent on the coronary vasculature are mediated by stimulation of prostaglandin synthesis. Thus it appears that prostaglandin synthesis plays an integral role In both the maintenance of coronary vascular tone and the autoregulatory response in isolated rabbit hearts.