Changes in coronary endothelial cell Ca2+ concentration during shear stress- and agonist-induced vasodilation

Increases in intraluminal shear stress are thought to cause vasodilation of coronary arterioles by activation of Ca2+-dependent endothelial nitric oxi de synthase followed by release of nitric oxide. We tested the hypothesis t hat endothelium-dependent vasodilation of isolated coronary arterioles to s hear stress and agonists is necessarily preceded by an increase in endothel ial cell Ca2+ concentration ([Ca2+](i)). After selective loading of endothe lium in isolated rabbit coronary arterioles with fura 2, simultaneous chang es in diameter and [Ca2+](i) were recorded. Vasodilations recorded in respo nse to ACh, substance P, or shear stress were accompanied by significant in creases in endothelial cell [Ca2+](i). Vasodilations to shear stress were a ccompanied by smaller changes in endothelial cell [Ca2+](i) than equivalent dilations evoked by substance P or ACh. To test the role for Ca2+ as an ac tivator of endothelial nitric oxide synthase, the endothelium was treated w ith the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N, N, N', N'-tetraaceti c acid. 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid eliminated significant changes in endothelial cell [Ca2+](i) and inhibited dilations to ACh and substance P but did not significantly affect shear stress-induce d vasodilation. The data indicate that endothelium-dependent vasodilation o f coronary arterioles in response to agonists and shear stress is mediated in part through a rise in endothelial cell [Ca2+](i) but that a substantial component of the shear stress-induced response occurs through a Ca2+-insen sitive pathway.