Cardiac inotropic effects of leukotriene C4 and prostaglandin I2 in the unanesthetized American bullfrog, Rana catesbeiana

Abstract

The cardiovascular effects of leukotriene (LT) C4 and prostaglandin (PG) I2 were compared in the unanesthetized American bullfrog, Rana catesbeiana. Bullfrogs were instrumented to measure mean arterial pressure, peak ventricular pressure, its derivative (VP + dP/dt), and heart rate. Two hours after recovery from anesthesia, intravenous injections of LTC4 or PGI2 were tested over a dose range from 0.003 to 3 micrograms/kg body weight (bw). Both eicosanoids decreased mean arterial pressure, systolic ventricular pressure, and its derivative (VP + dP/dt). The effects of LTC4 and PGI2 on all parameters were similar at doses below 3 micrograms/kg bw. However, at 3 micrograms/kg bw, LTC4 had more potent negative inotropic effects than PGI2. Both compounds increased heart rate at 0.3 microgram/kg bw, but at 3 micrograms/kg bw PGI2 caused greater increases than LTC4. The hypotensive and negative inotropic effects of LTC4 were blunted in animals pretreated with indomethacin (4 mg/kg bw) to prevent endogenous prostaglandin and thromboxane synthesis, whereas the cardiovascular effects of PGI2 were unaffected by the blockade. The data show that both eicosanoids have similar qualitative effects on blood pressure and cardiac performance. However, the effects of LTC4 may be partially mediated by release of endogenous cyclooxygenase products, possibly PGI2. These results suggest that the bullfrog, an animal with no coronary arteries, is a useful model for comparative studies of cardiac actions of eicosanoids which are independent of effects mediated by changes in coronary vascular resistance.