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 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.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D009924:Organ Culture Techniques; D011817:Rabbits; D013314:Stress, Mechanical; D013373:Substance P / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology