ELEVATION OF INTRACELLULAR CALCIUM IN SMOOTH-MUSCLE CAUSES ENDOTHELIAL-CELL GENERATION OF NO IN ARTERIOLES

It is well known that vascular smooth muscle tone can be modulated by signals arising in the endothelium (e.g., endothelium-derived relaxing factor, endothelium-derived hyperpolarizing factor, and prostaglandin s), Here we show that during vasoconstriction a signal can originate i n smooth muscle cells and act on the endothelium to cause synthesis of endothelium-derived relaxing factor, We studied responses to two vaso constrictors (phenylephrine and KCI) that act by initiating a rise in smooth muscle cell intracellular Ca2+ concentration ([Ca2+](i)) and ex ert little or no direct effect on the endothelium, Fluo-3 was used as a Ca2+ indicator in either smooth muscle or endothelial cells of arter ioles from the hamster cheek pouch. Phenylephrine and KCI caused the e xpected rise in smooth muscle cell [Ca2+](i) that was accompanied by a n elevation in endothelial cell [Ca2+](i). The rise in endothelial cel l [Ca2+](i) was followed by increased synthesis of NO, as evidenced by an enhancement of the vasoconstriction induced by both agents after b lockade of NO synthesis, The molecule involved in signal transmission from smooth muscle to endothelium is as yet unknown. However, given th at myoendothelial cell junctions are frequent in these vessels, we hyp othesize that the rise in smooth muscle cell Ca2+ generates a diffusio n gradient that drives Ca2+ through myoendothelial cell junctions and into the endothelial cells, thereby initiating the synthesis of NO.