Cardiovascular effects of leukotrienes in the bullfrog

While the cardiovascular effects of the sulfidopeptide leukotrienes (LTs) have been well studied in mammals, their effects are not well known in lower vertebrates. American bullfrogs (Rana catesbeiana) were cannulated in the right sciatic artery and left sciatic vein. In some studies an additional ventricular cannula was implanted. LTC4, LTD4, and LTE4 were compared for their cardiovascular actions by infusion via the sciatic vein into the unanesthetized animals. While all three leukotrienes decreased mean arterial pressure (MAP) and increased heart rate (HR), LTC4 was found to be more potent than the other leukotrienes. In bullfrogs with ventricular cannulae to measure ventricular pressure (VP) and its derivative (+ dP/dt), LTC4 had negative inotropic effects which were blunted by indomethacin (4 mg/kg-bw). 3H-LTC4 metabolism studies were carried out using blood and plasma to examine conversion to other products. Following incubation for 12 min and extraction by C18 Sep-Pak cartridges, samples were analyzed by high performance liquid chromatography. In whole blood, but not in plasma, 3H-LTC4 was rapidly converted to a compound with the retention time of the LTD4 standard. Little conversion to LTE4 was observed within the time course of the experiment. The data suggest that cardiovascular effects of LTC4 may be greater than those observed, since LTC4 is rapidly metabolized to a less active compound. The effects of LTC4 may, in part, be due to stimulation of synthesis of cyclooxygenase metabolites. The ability to record the effects of leukotrienes uncomplicated by effects on coronary arteries make the bullfrog an excellent model for comparative studies on the cardiovascular effects of leukotrienes.