THE CARDIAC EFFECTS OF PROSTAGLANDINS AND THEIR MODIFICATION BY THE PROSTAGLANDIN ANTAGONIST N-0164

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  • 1 January 1980
    • journal article
    • research article
    • Vol. 214  (1) , 45-49
Abstract
The cardiac actions of a number of prostaglandins [PG] and their modification by the PG antagonist sodium p-benzyl-4[1-oxo-2-(4-chlorobenzyl)-3-phenyl propyl]phenyl phosphonate (N-0164) was studied in the isolated guinea-pig heart. Arachidonic acid, PGE2 (0.01-1 .mu.g) and prostacyclin PGI2 (0.01-10 .mu.g), administered by bolus injection, caused dose-dependent increases in coronary flow rate, but PGD2, PGF2.alpha. and the stable PG enderoperoxide analog U46619 (0.01-100 .mu.g) caused dose-dependent decreases in coronary flow rate. Over the dose range studied, PGE2 arachidonic acid, PGI2 and PGF2.alpha. increased the sinus rate and PGD2 decreased the sinus rate, but U46619 had no consistent effect. Arachidonic acid, PGF2.alpha., PGD2 and U46619 produced a decrease in ventricular contractile force, but PGE2 had no effect and PGI2 produced a modest increase in ventricular contractile force. N-0164 (10 ng and 100 ng/ml) selectively antagonized the coronary vasoconstrictor effects of PGD2 and PGF2.alpha.. N-0164, at higher concentrations (1 .mu.g/ml), antagonized the coronary vasodilator actions of PGE2; it did not modify the coronary vasodilator action of PGI2 N-0164 (10-100 ng/ml) antagonized as a function of its concentration sinus rate changes produced by PGD2 or PGF2.alpha., whereas at higher concentrations (1 .mu.g/ml), rather than antagonizing, it potentiated sinus rate increases produced by PE2 or PGI2. The cardiac actions of PG are complex and are not readily elucidated by the use of the PG antagonist N-0164.