Microcirculatory effects of leukotrienes, LTC4 and LTD4, in rat cremaster muscle

Studies were performed to determine the vasomotor effects of leukotrienes, LTC4 and LTD4, on rat cremaster third-order arterioles and the effects of PGE2 on arteriolar responsiveness to LTC4. Five to six week-old male rats were anesthetized with sodium pentobarbital (35 mg/kg) and the left cremaster muscle exteriorized and prepared for in vivo television microscopy. Measurement of changes in arteriolar internal diameters was performed with an electronic image shearing device under control conditions and during the topical administration of vasoactive substances before and after the suffusion, onto the surface of the cremaster muscle, of either indomethacin (IND, 10 ug/ml) or 5,8,11,14-eicosatetraynoic acid (ETYA, 20 ug/ml). LTC4 and LTD4 were found to evoke equivalent, dose-dependent arteriolar constrictions, in the dose range of 2 pg to 2 ng, and concomitant decreases in microvascular blood flow. The application of either IND or ETYA, to the cremaster muscle did not significantly effect control diameters nor the constrictor responses to leukotrienes. While the principal action of the two leukotrienes was vasoconstriction, small dilator responses were occasionally observed that were also not affected by IND or ETYA. PGE2 did not inhibit the arteriolar constrictor responses to LTC4. The current observations indicate that LTC4 and LTD4 are extremely potent arteriolar constrictor agents in skeletal muscle and that their vascular effects are not mediated or modulated by products of the cyclooxygenase or lipoxygenase pathway of arachidonic acid metabolism.