Nerve‐induced smooth muscle to endothelium signaling in small resistance arteries

Abstract

Communication from endothelial cell (EC) to vascular smooth muscle cell (VSMC) has been shown to play a pivotal role in the maintenance of vascular tone. Despite emerging evidence that the converse pathway ‐ signaling from VSMCs to ECs ‐ may be important for feedback regulation of arterial diameter, the effects of nerve stimulation on EC calcium (Ca2+) dynamics are not known. Utilizing a transgenic mouse model in which the Ca2+ biosensor, GCaMP2, is expressed specifically in vascular ECs, we investigated the novel concept of nerve/VSMC to EC signaling. Here, we present the first evidence that electrical field stimulation (EFS) of sympathetic nerves causes a dramatic elevation of local EC Ca2+ signals (“pulsars”) in endothelial projections to SM as well as in Ca2+ waves in small resistance mesenteric arteries. Blocking VSMC purinergic and adrenergic receptors differentially affects the time course of the EFS‐induced elevation in EC Ca2+, suggesting that the early response to EFS requires activation of SM P2X1Rs and the delayed response requires SM alpha adrenergic receptors. Inhibition of EC intermediate conductance, calcium‐sensitive K+ (IK) channels enhances nerve‐evoked vasoconstriction. These data are consistent with a novel negative feedback mechanism whereby sympathetic nerve stimulation increases EC Ca2+ and IK channel activity to oppose SM activation. (Supported by the NIH).