The cardiac effects of prostaglandins and their modification by the prostaglandin antagonist N-0164.
The cardiac actions of a number of prostaglandins and their modification by the prostaglandin 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, prostaglandin (PG)E2 (0.01--1 micrograms) and prostacyclin (0.01--10 micrograms), administered by bolus injection, caused dose-dependent increases in coronary flow rate, whereas PGD2, PGF2 alpha and the stable PG enderoperoxide analog U46619 (0.01--100 micrograms) caused dose-dependent decreases in coronary flow rate. Over the dose range studied, PGE2, arachidonic acid, prostacyclin and PGF2 alpha increased the sinus rate and PGD2 decreased the sinus rate, whereas U46619 had no consistent effect. Arachidonic acid, PGF2 alpha, PGD2 and U46619 produced a decrease in ventricular contractile force, whereas PGE2 had no effect and prostacyclin 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 micrograms/ml), antagonized the coronary vasodilator actions of PGE2; however, it did not modify the coronary vasodilator action of prostacyclin. N-0164 (10--100 ng/ml) also antagonized as a function of its concentration sinus rate changes produced by either PGD2 or PGF2 alpha, whereas at higher concentrations (1 microgram/ml), rather than antagonizing it potentiated sinus rate increases produced by either PGE2 or prostacyclin. These results suggest that the cardiac actions of prostaglandins are complex and are not readily elucidated by the use of the prostaglandin antagonist, N-0164.
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D011453:Prostaglandins / Q000494:pharmacology*; D011457:Prostaglandins D / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors
D001095:Arachidonic Acids; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D011457:Prostaglandins D; D011458:Prostaglandins E; D011460:Prostaglandins F; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C012641:N 0164; D011464:Epoprostenol