The effects of arachidonic acid in isolated atria of guinea pigs.

The effects of free and albumin-bound arachidonic acid, which is the precursor of the prostaglandins E2 and F2alpha, were studied on the spontaneous rate, contractile force and myocardial fatty acid metabolism in isolated, spontaneously beating atria of guinea pigs. Both free and albumin-bound arachidonic acid (10(-6)-10(-3) M) produced a dose-dependent positive chronotropic and a modest inotropic action. Tachyphylaxis to the positive chronotropic action of arachidonic acid developed in the course of repeated applications. Beta-Adrenoceptor blockade (pincolol) and pretreatment with reserpine or prostaglandin-synthetase inhibitors (indomethacin, fenoprofen, aspirin, 5,8,11,14-eicosatetraynoic acid) failed to affect the chronotropic activity of arachidonic acid significantly. The action of arachidonic acid was independent of the decarboxylation of the fatty acid. Linoleic and oleic acids did not show any positive chronotropic activity. The data are interpreted as suggesting that changes induced by arachidonic acid might be partly due to peroxides formed from arachidonic acid.