Effects of arachidonic acid and bradykinin on the coronary flow, release of PGI2 and cardiac functions in the perfused guinea-pig heart.

Abstract

The contribution of prostacyclin (PGI2) to the coronary vasodilating action of arachidonic acid (AA) and bradykinin (BK) was examined in isolated perfused guinea pig hearts. The injection of AA (100-1000 ng) and BK (1-100 ng) into the heart resulted in a dose-dependent increase in the total amount of coronary flow and a release of 6-keto-prostaglandin [PG] F1.alpha., a stable metabolite of PGI2. Both AA and BK showed weak positive chronotropic effects. Higher doses (300 and 1000 ng) of AA caused a transient reduction in the coronary flow rate, left ventricular systolic pressure, and left ventricular dp/dt [change in pressure over line]. The changes in coronary flow, release of PGI2 and all cardiodynamic parameters induced by AA were abolished by pretreatment of the preparation with diclofenac-sodium. BK-induced increase in coronary flow rate was only partially reduced by diclofenac-sodium, when the release of 6-keto-PG F1.alpha. was completely inhibited. Evidently, in isolated perfused guinea pig hearts, BK has both PGI2-independent and PGI2-dependent coronary vasodilating actions; the latter action is < 25%, and the coronary vasodilating action of AA is mainly mediated by PGI2.