Divalent cation regulation of endothelial-dependent relaxation in coronary blood vessels

In the present study, effects of divalent cations, magnesium (Mg), calcium (Ca), barium (Ba) and strontium (Sr), in the regulation of the expression of endothelium-derived relaxant factor(s) (EDRF) in isolated canine coronary arteries were studied. Ca was found to stimulate, while Mg inhibits, the basal release of EDRF, such that a lowering of extracellular Mg (0-Mg) resulted in an "unmasking" of Ca-induced endothelium (EDRF)-dependent relaxation. Inhibition of the basal release of EDRF by the removal of extracellular Ca (0-Ca), in the latter 0-Mg condition, resulted in a complete reversal of the observed relaxation to a vasoconstriction. Reactivation of EDRF, in the latter 0-Ca and 0-Mg condition, with the re-addition of Ca (0.01-1.75 mM) again resulted in a dose- and endothelium-dependent relaxation with an ED50 of approx. 0.1 mM Ca. Sr (0.01-1.0 mM), but not Ba, was found to be equieffective as Ca in the activation of EDRF in this 0-Ca and 0-Mg condition and produced a similar dose- and endothelium-dependent relaxation. In endothelium-disrupted coronary arteries, however, both Sr and Ba were capable of mimicking Ca in producing a direct vascular smooth muscle cell contraction, as has been reported previously. These results demonstrate that divalent cations, in addition to their direct role in the regulation of vascular smooth muscle cell contraction, also play an important regulatory role in the expression of endothelium-dependent relaxation in coronary blood vessels.