Abstract
A potential "new player" in arteries for mediating shear stress responses is the epithelial Na(+ )channel (ENaC). The contribution of ENaC as shear sensor in intact arteries, and particularly different types of arteries (conduit and resistance), is unknown. We investigated the role of ENaC in both conduit (carotid) and resistance (third-order mesenteric) arteries isolated from C57B1/6J mice. Vessel characteristics were determined at baseline (60 mmHg, no flow) and in response to increased intraluminal pressure and shear stress using a pressure myograph. These protocols were performed in the absence and presence of the ENaC inhibitor amiloride (10 mu M) and after inhibition of endothelial nitric oxide synthase (eNOS) by N-omega-nitro-L-arginime methyl ester (L-NAME; 100 mu M). Under no-flow conditions, amiloride increased internal and external diameters of carotid (13 +/- 2%. P < 0.05) but not mesenteric (0.5 +/- 0.9%. P > 0.05) arteries. In response to increased intraluminal pressure, amiloride had no effect on the internal diameter of either type of artery. However, amiloride affected the stress-strain curves of mesenteric arteries. With increased shear stress, ENaC-dependent effects were observed in both arteries. In carotid arteries, amiloride augmented flow-mediated dilation (9.2 +/- 53%) compared with control (no amiloride, 6.2 +/- 3.3%, P < 0.05). In mesenteric arteries, amiloride induced a flow-mediated constriction (-115 +/- 6.6%) compared with control (-2.2 +/- 45%. P < 0.05). L-NAME mimicked the effect of ENaC inhibition and prevented further amiloride effects in both types of arteries. These observations indicate that ENaC contributes to shear sensing in conduit and resistance arteries. ENaC-mediated effects were associated with NO production but may involve different (artery-dependent) downstream signaling pathways.
NEW & NOTEWORTHY The epithelial Na(+ )channel (ENaC) contributes to shear sensing in conduit and resistance arteries. In conduit arteries ENaC has a role as a vasoconstrictor, whereas in resistance arteries ENaC contributes to vasodilation. Interaction of ENaC with endothelial nitric oxide synthase/nitric oxide signaling to mediate the effects is supported; however, cross talk with other shear stress-dependent signaling pathways cannot be excluded.