ASIC2 protein is required for pressure‐induced constriction in mouse renal interlobar artery

Abstract

Pressure‐induced, or myogenic, constriction is a mechanically mediated event. Increased luminal pressure stretches vascular walls leading to the opening of presumptive mechanosensitive channels, and initiating the cascade for vascular contraction. Epithelial Na+ Channel and Acid Sensing Ion Channel 2 (ASIC2) proteins may form mechanosensitive channels. Myogenic constriction may protect against pressure‐induced renal injury. ASIC2 heterozygous (+/‐) mice have no cerebral myogenic response; however renal myogenic response and susceptibility to renal injury remains unknown. The current goal was to investigate the role of ASIC2 in renal interlobar arteries and renal injury. We examined agonist‐ and pressure‐induced constriction in isolated renal interlobar arteries from ASIC2 wildtype (+/+) and +/‐ mice. Constriction to KCl (20 ‐ 80 mM) and phenylephrine (10−7 ‐ 10−4 M) was not different. Constrictor responses to intraluminal pressure (25 ‐ 150 mmHg) were significantly impaired in ASIC2 +/‐ mice (31.6 + 3.7 and 2.4 + 1.2% myogenic tone at 150 mmHg in +/+ and +/‐ ASIC2 mice). Histological analysis demonstrated tubular casts and a 5‐fold increase in renal macrophage infiltration suggestive of renal injury in ASIC2 +/‐ mice. These results indicate normal ASIC2 is required for myogenic constriction in the renal interlobar artery and may protect against pressure‐induced injury. Supported by NIH‐NHLBI & NINDS.