ADRENOMEDULLIN DECREASES BOTH CYTOSOLIC CA2+ CONCENTRATION AND CA2+-SENSITIVITY IN PIG CORONARY ARTERIAL SMOOTH-MUSCLE

Adrenomedullin (AM) is a newly identified vasorelaxant peptide which circulates in human plasma. We investigated the cellular mechanisms of AM-induced relaxation in the pig coronary artery, using fura-2 fluorometry and receptor-coupled membrane permeabilization by alpha-toxin. AM inhibited both the elevations of cytosolic Ca2+ concentration ([Ca2+]i) and the tension induced by high K+-depolarization and by U46619. The extent of the tension inhibition was much greater than expected based on the extent of reductions of [Ca2+]i. Thus, the [Ca2+]i (abscissa)-tension (ordinate) relation shifted to the right by AM. In alpha-toxin-permeabilized strips, AM decreased the tension development at constant [Ca2+]i (pCa 6.5) in the presence of GTP, whereas GDP beta S antagonized this effect. We thus conclude that AM relaxes the coronary artery not only by decreasing [Ca2+]i but also by decreasing the Ca2+-sensitivity of the contractile apparatus, as mediated by G-protein. (C) 1995 Academic Press, Inc.