Indomethacin and meclofenamate potentiation of skeletal muscle active hyperemia.

The effects of indomethacin and meclofenamate on active hyperemia following sustained, maximal isometric contractions were studied in free-flowing dog gracilis muscles. Muscles were stimulated to contract in situ for 1, 4, 7, and 10 s durations in the absence and presence of indomethacin (62.5 micrograms/ml blood), meclofenamate (50 micrograms/ml blood), or appropriate vehicles. Drugs were administered by continuous intra-arterial infusion into the muscle. Cyclo-oxygenase inhibition was verified by intra-arterial injection of arachidonic acid. Resting vascular conductance decreased by 28% with meclofenamate but not with indomethacin. Meclofenamate and indomethacin increased active hyperemia excess flows by 49% and 101%, respectively, following 10 s of contraction. These results differ markedly from previous studies. We suggest that non-specific actions of both drugs, unrelated to their effect on prostaglandin synthesis, result in potentiation of normal vasodilator responses to muscle contraction.