Effect of PGD2 on cardiac contractility: a negative inotropism secondary to coronary vasoconstriction conceals a primary positive inotropic action.
The purpose of this study was to characterize by pharmacological means the inotropic action of prostaglandin D2 (PGD2) in the guinea-pig heart. In the whole heart perfused at constant pressure, PGD2 (0.01-10 micrograms) reduced coronary flow rate and decreased left ventricular contractile force in a dose-dependent manner. When the coronary vasoconstricting effect of PGD2 was antagonized by the PG antagonist sodium p-benzyl-4[1-oxo-2-(4-chlorobenzyl)-3-phenyl propyl]phenyl phosphonate (N-0164), by the cyclooxygenase inhibitor indomethacin or by the thromboxane synthetase inhibitor sodium (E)-3-[4-(1-imidazolyl-methyl)phenyl]-2-propanoate (OKY 046), the negative inotropic response to PGD2 was attenuated or completely abolished and a positive inotropic effect was unmasked. In the isolated left atrium or right ventricular papillary muscle preparations, PGD2 induced only a positive inotropic response. The atrial response to PGD2 was unaffected by N-0164, indomethacin or propranolol but was markedly decreased by carbachol or adenosine. Conversely, the response of the papillary muscle to PGD2 was potentiated by papaverine. Thus, these data indicate that PGD2 has a primary positive inotropic effect, which may involve cyclic AMP metabolism. On the other hand, because PGD2 is also a potent coronary vasoconstrictor, the secondary negative inotropic effect of PGD2 predominates.
D000818:Animals; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000187:drug effects*; D000242:Cyclic AMP / Q000502:physiology; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D010972:Platelet Activating Factor; D015230:Prostaglandin D2; D011457:Prostaglandins D / Q000494:pharmacology*; D013189:SRS-A / Q000494:pharmacology; D013268:Stimulation, Chemical; D014661:Vasoconstriction / Q000187:drug effects*
D008689:Methacrylates; D010972:Platelet Activating Factor; D011457:Prostaglandins D; D013189:SRS-A; D000242:Cyclic AMP; C034364:ozagrel; D015230:Prostaglandin D2; D007213:Indomethacin