Loss of smooth muscle βENaC induces hypertension

Myogenic autoregulation of renal blood flow has been proposed to protect delicate glomerular capillaries from barotrauma. Previous studies from our laboratory have shown that mice lacking normal levels of βENaC globally, i.e. hypomorph mice, display a loss of myogenic constriction in renal interlobar arteries and afferent arterioles, but not vasoconstriction per se. The mice also display a loss of renal myogenic autoregulation of blood flow and mild renal injury. Despite reported defects in renal sodium handling, we found βENaC hypomorphic mice were mildly hypertensive; mean arterial blood pressure was elevated 10-15 mm Hg, as measured by radiotelemetry. To determine the importance of smooth muscle βENaC in this phenotype, we generated a smooth muscle βENaC knockout mouse by crossing βENaC floxed mice with SM22-Cre mice. We confirmed loss of βENaC in vascular smooth muscle cells using confocal microscopy in dissociated renal VSMCs. We then measured systolic blood pressure (SBP) by tail-cuff plethysmography from every two weeks from 6 – 26 weeks of age in male and female mice (n=8-9/group). Prior to SBP assessment, we acclimated the mice to the restrainer and cuff inflation on alternate days for one week. SBP was elevated in Cre+ male and female mice from 14 weeks of age, compared to Cre- littermates. By 26 weeks of age, SBP was greater in Cre+ male (139±2 vs 119±1) and female (135±2 vs 115±4) mice. We also assessed heart and kidney masses at 26 weeks of age. We found heart and kidney masses normalized to body mass were increased in male Cre+ mice, p < 0.05. Studies on the assessment of renal injury using histological assessment and western blot analysis are ongoing. These findings confirm that the BP phenotype of smooth muscle βENaC knockout mice is similar to global βENaC hypomorphic mice. R01DK137167, P30GM149404, P20GM104357, 5T32HL105324, and P20GM121334 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.