Changes in coronary endothelial cell Ca21 concentration during shear stress- and agonist-induced vasodilation

Muller, Judy M., Michael J. Davis, Lih Kuo, and William M. Chilian. Changes in coronary endothelial cell Ca21 concentration during shear stressand agonist-induced vasodilation. Am. J. Physiol. 276 (Heart Circ. Physiol. 45): H1706–H1714, 1999.—Increases in intraluminal shear stress are thought to cause vasodilation of coronary arterioles by activation of Ca21-dependent endothelial nitric oxide synthase followed by release of nitric oxide. We tested the hypothesis that endothelium-dependent vasodilation of isolated coronary arterioles to shear stress and agonists is necessarily preceded by an increase in endothelial cell Ca21 concentration ([Ca]i). After selective loading of endothelium in isolated rabbit coronary arterioles with fura 2, simultaneous changes in diameter and [Ca]i were recorded. Vasodilations recorded in response to ACh, substance P, or shear stress were accompanied by significant increases in endothelial cell [Ca]i. Vasodilations to shear stress were accompanied by smaller changes in endothelial cell [Ca]i than equivalent dilations evoked by substance P or ACh. To test the role for Ca21 as an activator of endothelial nitric oxide synthase, the endothelium was treated with the Ca21 chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N8,N8-tetraacetic acid. 1,2-Bis(2-aminophenoxy)ethane-N,N,N8,N8-tetraacetic acid eliminated significant changes in endothelial cell [Ca]i and inhibited dilations to ACh and substance P but did not significantly affect shear stress-induced vasodilation. The data indicate that endothelium-dependent vasodilation of coronary arterioles in response to agonists and shear stress is mediated in part through a rise in endothelial cell [Ca]i but that a substantial component of the shear stress-induced response occurs through a Ca21-insensitive pathway.