Increases in intraluminal shear stress are thought to cause vasodilation of coronary arterioles by activation of Ca²⁺-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 Ca²⁺ concentration ([Ca²⁺]_i). After selective loading of endothelium in isolated rabbit coronary arterioles with fura 2, simultaneous changes in diameter and [Ca²⁺]_i were recorded. Vasodilations recorded in response to ACh, substance P, or shear stress were accompanied by significant increases in endothelial cell [Ca²⁺]_i. Vasodilations to shear stress were accompanied 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 activator of endothelial nitric oxide synthase, the endothelium was treated with the Ca²⁺ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic 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-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 [Ca²⁺]_i but that a substantial component of the shear stress-induced response occurs through a Ca²⁺-insensitive pathway.

calcium; 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; nitric oxide; nitric oxide synthase; isolated arterioles

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