title: Altered whole kidney blood flow autoregulation in a mouse model of reduced beta-ENaC.
abstract: Renal blood flow (RBF) autoregulation is mediated by at least two mechanisms, the fast acting myogenic response (approximately 5 s) and slow acting tubuloglomerular feedback (TGF; approximately 25 s). Previous studies suggest epithelial Na(+) channel (ENaC) family proteins, beta-ENaC in particular, mediate myogenic constriction in isolated renal interlobar arteries. However, it is unknown whether beta-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 beta-ENaC (m/m). To address this goal, we evaluated the temporal response of RBF and renal vascular resistance (RVR) to a 2-min 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 approximately 50% in m/m mice, indicating the speed of the myogenic response was inhibited. Steady-state autoregulation was similar between beta-ENaC +/+ and m/m mice. Although the rate of the secondary increase in RVR, attributed to TGF, was similar in beta-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 beta-ENaC is an important mediator of renal myogenic constriction-mediated RBF autoregulation in vivo.
authors.affiliation: Department of Physiology and Biophysics and the Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, USA.
authors.forename: Samira C
authors.initials: SC
authors.lastname: Grifoni
authors.forename: Rumbidzayi
authors.initials: R
authors.lastname: Chiposi
authors.forename: Susan E
authors.initials: SE
authors.lastname: McKey
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ryan
authors.forename: Heather A
authors.initials: HA
authors.lastname: Drummond
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D015536:Down-Regulation; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D025461:Feedback, Physiological; D006439:Hemodynamics; D006706:Homeostasis; D007678:Kidney Glomerulus / Q000502:physiology; D007684:Kidney Tubules / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D012079:Renal Circulation / Q000502:physiology*; D013997:Time Factors; D014655:Vascular Resistance / Q000502:physiology
chemical_list: D053503:Epithelial Sodium Channels