The stimulation of cardiac prostaglandin production by blood plasma and its relationship to the regulation of coronary flow in isolated isovolumic rabbit hearts.

Infusion of small amounts of blood plasma into isolated, isovolumic rabbit hearts perfused with Tyrode's solution resulted in coronary vasoconstriction followed by a decrease in left ventricular developed pressure and dP/dt. Maximal effects were obtained with a perfusate plasma concentration of 1%. Increasing the plasma concentration beyond 1% did not appreciably increase the coronary vasoconstriction. During perfusion with 2% plasma, the coronary flow-oxygen uptake ratio was unchanged over a range of perfusion pressures (40-100 mm Hg) and vascular resistance increased with pressure. In the absence of plasma, the coronary flow-oxygen uptake ratio increased with pressure and vascular resistance decreased. Thus, cardiac regulation of coronary flow in response to changes in perfusion pressure occurred in the presence of plasma but not in its absence. The effects of plasma were reduced with two different inhibitors of prostaglandin synthesis (5,9,11,14-eicosatetraynoic acid and indomethacin). At a perfusate concentration of 50 mug/ml, indomethacin abolished the effects of 2% plasma. Rat stomach strip bioassay for prostaglandin activity indicated that the vasoconstrictor effect of plasma was accompanied by a 4-fold increase in the release of prostaglandin activity by the isolated hearts. The vasoconstrictor effect of plasma also was accompanied by an increase in the conversion of 3H-arachidonate to radiolabeled prostaglandins E2 and F2alpha. These results indicate that a relationship exists between a coronary vasoconstrictor in plasma, cardiac prostaglandin synthesis, and the regulation of coronary flow in response to changes in perfusion pressure in isolated rabbit hearts.