POSITIVE INOTROPIC AND CHRONOTROPIC EFFECTS OF BERAPROST SODIUM, A STABLE ANALOG OF PROSTACYCLIN, IN ISOLATED GUINEA-PIG MYOCARDIUM

1. Inotropic and chronotropic effects of beraprost sodium (betaprost), a chemically stable prostacyclin analogue, were examined in isolated myocardial preparations of guinea pigs. 2. In the left atria, 10(-9)-1 0(-7) M beraprost had no significant effect on the contractile force, but 10(-6) and 10(-5) M produced a concentration dependent positive in otropic response. This effect was antagonized by S-145, a potent and s elective thromboxane A(2) (TXA(2)) receptor antagonist, but not by pro pranolol. 3. Beraprost, from 10(-9) to 10(-5) M, had no significant in otropic effect in the right ventricular papillary muscles. 4. In the r ight atria, 10(-9) and 10(-8) M beraprost had no significant effect, b ut 10(-7)-10(-5) M caused an increase in beating rate; this effect was not affected by S-145. 5. The present study demonstrates that berapro st has positive inotropic and chronotropic effects at high doses on is olated guinea pig atria. The inotropic effect may be mediated by the T XA(2) receptor, but some mechanism other than the TXA(2) receptor is r esponsible for the chronotropic effect.