Epithelial Na + channel differentially contributes to shear stress-mediated vascular responsiveness in carotid and mesenteric arteries from mice

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 314; no. 5; pp. H1022 - H1032
• Main Authors: Ashley, Zoe, Mugloo, Sama, McDonald, Fiona J, Fronius, Martin
• Format: Journal Article
• Language: English
• Published: United States 01.05.2018
• Subjects: Animals; Arterial Pressure; Carotid Arteries - drug effects; Carotid Arteries - metabolism; Epithelial Sodium Channel Blockers - pharmacology; Epithelial Sodium Channels - drug effects; Epithelial Sodium Channels - metabolism; In Vitro Techniques; Male; Mechanotransduction, Cellular - drug effects; Mesenteric Arteries - drug effects; Mesenteric Arteries - metabolism; Mice, Inbred C57BL; Nitric Oxide - metabolism; Nitric Oxide Synthase Type III - metabolism; Regional Blood Flow; Stress, Physiological; Vasoconstriction - drug effects; Vasodilation - drug effects; conduit arteries; epithelial sodium channel; resistance arteries; flow-mediated response
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00506.2017

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 C57Bl/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 µM) and after inhibition of endothelial nitric oxide synthase (eNOS) by N -nitro-l-arginine methyl ester (l-NAME; 100 µM). 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 ± 5.3%) compared with control (no amiloride, 6.2 ± 3.3%, P < 0.05). In mesenteric arteries, amiloride induced a flow-mediated constriction (-11.5 ± 6.6%) compared with control (-2.2 ± 4.5%, 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.