Metabolism and cardiovascular effects of leukotrienes in the marine toad Bufo marinus

Leukotriene (LT) metabolism and physiology have been studied extensively in mammals; however, little is known of their roles in nonmammalian vertebrates. This study examines the cardiovascular effects of leukotrienes on blood pressure and heart rate in the conscious and cannulated marine toad, Bufo marinus. The sulfidopeptide leukotrienes, LTC4, LTD4, and LTE4 elicited hypotension with equal potency. However, with respect to heart rate changes and duration of action, the responses to LTC4 and LTD4 were greater and lasted longer than those to LTE4. The nonpeptide leukotriene, LTB4, had significantly less potent effects on heart rate and blood pressure. The leukotriene-induced increases in heart rate with 1000 and 300 ng/kg body wt LTC4 and LTD4 were blocked with 5 mg/kg body wt propranolol, a beta-antagonist, suggesting sympathetic reflex regulation of heart rate. Metabolism of [3H]LTC4 to [3H]LTD4 and [3H]LTE4 occurred rapidly in blood, with complete conversion to [3H]LTE4 within 5 min. Conversion was slower in plasma, with 18.9 +/- 0.5% of the radioactivity associated with [3H]LTC4 still remaining after 120 min. The toad is more similar to mammals than the bullfrog with respect to the metabolism of leukotrienes. In contrast to mammals, leukotrienes have hypotensive effects in both toad and bullfrog, although the order of potency differs. The effectiveness of the sulfidopeptide leukotrienes in eliciting hypotension at low doses (1 ng/kg body wt) suggests that these compounds may be important cardiovascular regulators in the toad.