Sex differences in sodium transporter and channel expression in mice after angiotensin II infusion.

Female mice have a reduced blood pressure rise in response to angiotensin II (AII) infusion as compared to male mice. Furthermore, AII infusion into male rats has been shown to increase the renal protein abundance of the α‐subunit of the epithelial sodium channel (ENaC), while reducing density of β‐ENaC and the major band associated with γ‐ENaC (85 kDa), with no effect on the thiazide‐sensitive Na‐Cl cotransporter (NCC). We hypothesized that female mice might have reduced responsivity to AII with regard to changes in ENaC subunits as compared to male mice. To test this, 3‐month‐old male (M) and female (F) mice (C57Bl/6) received a sham surgery (C) or were implanted with osmotic minipumps to infuse 800 ng/kg/min AII (A) for 7 days (n = 6/sex/treatment). AII significantly increased band density for α‐ENaC in M and F mice (band density ~122% of MC), and the 70‐kDa band of γ‐ENaC (~145%), while reducing β‐ENaC (~58%) and the 85‐kDa band of γ‐ENaC (40–61%), similar to what has been seen in rats. There were no sex differences in the increases for α‐ and the 70‐kDa band of γ‐ENaC or in the decrease in β‐ENaC; however, the 85‐kDa band of γ‐ENaC fell significantly more in the M mice with AII infusion, i.e., band density (% MC): 40% (MA) and 61% (FA), suggesting greater activity in the males, of at least this subunit. In addition, female mice had increased renal abundance of endothelial nitric oxide synthase (with and without AII infusion) and NCC abundance (without AII infusion), a difference that was eliminated with AII infusion. In summary, with AII infusion, mice, like rats, have alterations in ENaC proteins associated with activation of the channel. Many changes were similar in males and females; however, males had a further reduction in the 85‐kDa band of γ‐ENaC which might indicate additional cleavage activation of this subunit.