Shear stress-induced vasodilation in porcine coronary conduit arteries is independent of nitric oxide release

The present study was performed to determine the importance of nitric oxide in eliciting epicardial coronary artery dilation during sustained increases in shear stress in the absence of pulsatile flow. Isolated first-order porcine epicardial coronary conduit arteries (∼500 μm) were preconstricted (U-46619) and subjected to steady-state changes in flow in vitro. Nonpulsatile flow (shear stress range from 0 to ∼100 dyn/cm²) produced a graded dilation of epicardial arteries. Inhibiting nitric oxide synthase with 10^-5 M N^ω-nitro-L-arginine methyl ester (L-NAME) blocked bradykinin-induced vasodilation but did not affect the flow-diameter relation or the maximum change in diameter from static conditions (67 ± 10 μm in control vs. 71 ± 8 μm after L-NAME, P = not significant). The addition of indomethacin (10^-5 M) had no effect on flow-mediated vasodilation. Depolarizing vascular smooth muscle with KCl (60 mM) or removing the endothelium blocked bradykinin vasodilation and completely abolished flow-mediated responses. The K⁺ channel blocker tetraethylammonium chloride (TEA; 10^-4M) attenuated flow-mediated vasodilation (maximum diameter change was 110 ± 18 μm under control conditions vs. 58 ± 10 μm after TEA, P < 0.001). These data indicate that epicardial coronary arteries dilate to steady-state changes in nonpulsatile flow via a mechanism that is independent of nitric oxide production. The ability to completely block this with KCl and attenuate it with TEA supports the hypothesis that epicardial coronary arteries dilate to steady levels of shear stress through hyperpolarization of vascular smooth muscle. This may be secondary to the release of an endothelium-dependent hyperpolarizing factor.