Impaired myogenic constriction of the renal afferent arteriole in a mouse model of reduced betaENaC expression

摘要

Previous studies demonstrate a role for beta epithelial Na~+ channel (betaENalphaC) protein as a mediator of myogenic constriction in renal interlobar arteries. However, the importance of PENaC as a mediator of myogenic constriction in renal afferent arterioles, the primary site of development of renal vascular resistance, has not been determined. We colocalized PENaC with smooth muscle alpha-actin in vascular smooth muscle cells in renal arterioles using immunofluorescence. To determine the importance of PENaC in myogenic constriction in renal afferent arterioles, we used a mouse model of reduced pENaC (betaENaC m/m) and examined pressure-induced constrictor responses in the isolated afferent arteri-ole-attached glomerulus preparation. We found that, in response to a step increase in perfusion pressure from 60 to 120 mmHg, the myogenic tone increased from 4.5 ± 3.7 to 27.3 ± 5.2% in +/+ mice. In contrast, myogenic tone failed to increase with the pressure step in m/m mice (3.9 ± 0.8 to 6.9 ± 1.4%). To determine the importance of PENaC in myogenic renal blood flow (RBF) regulation, we examined the rate of change in renal vascular resistance following a step increase in perfusion pressure in volume-expanded animals. We found that, following a step increase in pressure, the rate of myogenic correction of RBF is inhibited by 75% in PENaC m/m mice. These findings demonstrate that myogenic constriction in afferent arterioles is dependent on normal expression of PENaC.