METABOLISM AND CARDIOVASCULAR EFFECTS OF LEUKOTRIENES IN WARM-ACCLIMATED AND COLD-ACCLIMATED AMERICAN BULLFROGS (RANA-CATESBEIANA)

Sulfidopeptide leukotrienes are important mediators in mammals, but much less is known of their metabolism and action in nonmammalian vertebrates. This study examines the cardiovascular effects of leukotrienes on blood pressure and heart rate and compares the metabolism of leukotrienes in vivo and in vitro in warm- and cold-acclimated bullfrogs. Leukotriene C4 (LTC4) is more potent than leukotriene D4 (LTD4) and leukotriene E4 (LTE4) in eliciting hypotension. The leukotrienes are more potent in warm-acclimated animals. Conversion of [H-3]LTC4 to [H-3]LTD4 occurs rapidly in warm-acclimated bullfrogs, with 15.2 +/- 1.7% of the [H-3]LTC4 remaining at 1.5 min. Conversion is slower in vivo in cold-acclimated frogs, with 20.2 +/- 1.7% of the [H-3]LTC4 remaining by 6 min. In blood taken from warm-acclimated frogs, conversion of [H-3]LTC4 to [H-3]LTD4 occurs more rapidly at 22 than at 5-degrees-C. This pattern is similar in blood taken from cold-acclimated frogs, suggesting that no modification of gamma-glutamyl transpeptidase occurs at low temperature. [H-3]LTE4 production is not observed in vivo or in vitro during the time course of the experiments. The rapid metabolism of LTC4 to LTD4 may represent an inactivation mechanism in amphibians. The cardiovascular effects of LTC4 in vivo may be much greater than current measurements indicate because of rapid conversion of LTC4 to the less potent LTD4.