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Previous studies from our laboratory have suggested that degenerin proteins contribute to myogenic constriction, a mechanism of blood flow regulation and protection against pressure-dependent organ injury, in renal vessels. The goal of the present study was to determine the importance of one family member, acid-sensing ion channel 2 (ASIC2), in myogenic constriction of renal interlobar arteries, myogenic regulation of whole kidney blood flow, renal injury, and blood pressure using ASIC2+/+, ASIC2+/-, and ASIC2-/- mice. Myogenic constriction in renal interlobar arteries was impaired in ASIC2+/- and ASIC2-/- mice, whereas constriction to KCl/phenylephrine was unchanged. Correction of whole kidney renal vascular resistance RVR during the first 5 s after a 10- to 20-mmHg step increase in perfusion pressure, a timeframe associated with myogenic-mediated correction of RVR, was slowed 4.2 ± 0.9, 0.3 ± 0.7, and 2.4 ± 0.3 resistance units/s in ASIC2+/+, ASIC2+/-, and ASIC2-/- mice. Although modest reductions in function were observed in ASIC2-/- mice, greater reductions were observed in ASIC2+/- mice, which may be explained by protein-protein interactions of ASIC2 with other degenerins. Isolated glomeruli from ASIC2+/- and ASIC2-/- mice had modest alterations in the expression of inflammation and injury markers transforming growth factor-ß, mouse anti-target of antiproliferative antibody-1, and nephrin, whereas ASIC2+/- mice had an increase in the remodeling marker collagen type III. Consistent with a more severe loss of function, mean arterial pressure was increased in ASIC2+/- mice 131 ± 3 mmHg but not in ASIC2-/- mice 122 ± 3 vs. 117 ± 2 mmHg in ASIC2+/+ mice. These results suggest that ASIC2 contributes to transduction of the renal myogenic response and are consistent with the protective role of myogenic constriction against renal injury and hypertension. [ABSTRACT FROM AUTHOR]

Renal blood flow (RBF) autoregulation is mediated by at least two mechanisms, the fast acting myogenic response (∼5 s) and slow acting tubuloglomerular feedback (TGF; ∼25 s). Previous studies suggest epithelial Na+ channel (ENaC) family proteins, β-ENaC in particular, mediate myogenic constriction in isolated renal interlobar arteries. However, it is unknown whether β-ENaC-mediated myogenic constriction contributes to RBF autoregulation in vivo. Therefore, the goal of this investigation was to determine whether the myogenic mediated RBF autoregulation is inhibited in a mouse model of reduced β-ENaC (m/m). To address this goal, we evaluated the temporal response of RBF and renal vascular resistance (RVR) to a 2-mm step increase in mean arterial pressure (MAP). Pressure-induced changes in RBF and RVR at 0-5, 6-25, and 110-120 s after step increase in MAP were used to assess the contribution of myogenic and TGF mechanisms and steady-state autoregulation, respectively. The rate of the initial increase in RVR, attributed to the myogenic mechanism, was reduced by ∼50% in m/m mice, indicating the speed of the myogenic response was inhibited. Steady-state autoregulation was similar between β-ENaC +/+ and m/m mice. Although the rate of the secondary increase in RVR, attributed to TGF, was similar in β-ENaC +/+ and m/m mice, however, it occurred over a longer period (+ 10 s), which may have allowed TGF to compensate for a loss in myogenic autoregulation. Our findings suggest β-ENaC is an important mediator of renal myogenic constriction-mediated RBF autoregulation in vivo. [ABSTRACT FROM AUTHOR]