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Phenotyping a Mouse with Vascular Smooth Muscle Specific Deletion of the Gamma Subunit of the Epithelial Sodium Channel (γENaC)
Author(s) -
Hasan Mahpara,
Mutchler Stephanie,
Tan Roderick J,
Kohan Donald E,
Kleyman Thomas R
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.748.7
Subject(s) - epithelial sodium channel , endocrinology , vasoconstriction , medicine , kidney , blood pressure , myogenic contraction , renal function , electrical impedance myography , chemistry , sodium , vasodilation , smooth muscle , organic chemistry
The epithelial sodium channel (ENaC) has an important role in mediating myogenic tone of blood vessels. Previous studies found that mice with whole body knockdown of bENaC had an increased blood pressure, thought to be due to the loss of myogenic tone in the renal vasculature leading to inflammation and glomerular damage. However, because these results were obtained in an animal with global suppression of bENaC expression, the contributions of vascular smooth muscle (VSM) ENaC cannot be separated from effects of suppressed ENaC expression at other sites. To address this concern, we generated a VSM ENaC knockout animal using cre‐lox technology. Contrary to the bENaC hypomorphs, these mice did not have increased baseline blood pressure, as measured by radiotelemetry. Our preliminary results do not show significant differences in the myogenic response of the mesenteric or thoracodorsal arteries as assessed by pressure myography, however, the vessels do have greater angiotensin II‐mediated vasoconstriction. Preliminary results reveal that VSM ENaC KO mice exhibited increased glomerular filtration rate (GFR) at baseline, and that the knockouts had more proteinuria following a 4‐week treatment with high salt diet and aldosterone. However, wild type and VSM ENaC KO mice had similar responses to renal ischemia reperfusion injury, as assessed by serum creatinine and message levels for kidney injury markers NGAL and Kim1. Taken together, these data reveal that VSM gENaC may be playing a distinct role from that of bENaC, potentially only contributing to the myogenic response in the microvasculature of the kidney under conditions of stress. Support or Funding Information NIH P30 2P30DK079307‐11, NIH T32 2T32DK061296‐16 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .