Spironolactone Prevents Elevated Expression of Vascular ENaC in Hypertension

Epithelial sodium channel (ENaC) in the kidneys plays an important role in maintaining salt/water homeostasis and blood pressure. Recent research has demonstrated expression of ENaC in the vasculature, and a new role in regulation of the vascular tone. An increase in vascular tone is seen in vascular diseases such as hypertension indicating that changes in ENaC expression in the vasculature may contribute to hypertension. In this study, we hypothesized ENaC expression in arteries will increase in hypertension and that the treatment with antihypertensive drug, spironolactone (spiro‐) will reduce ENaC expression in arteries. Conduit (aorta) and resistance (mesenteric) arteries from male transgenic rats (Cyp1a1‐ren2) with diet‐inducible hypertension (0.167% indole‐3‐carbinol) were isolated and a‐, b‐ and g‐ENaC expression was analyzed by qRT‐PCR. Arteries from four animal groups were analyzed: (1) normotensive (2) hypertensive, (3) normotensive spiro‐ and (4) hypertensive spiro. Rats were fed a control or hypertensive diet for 6 weeks and in two groups (3 & 4) spiro‐ (4.41mg/kg/day) was introduced 2 weeks after the start of the diet. In mesenteric arteries of hypertensive animals a significant increase in both a‐ENaC (p=0.02) and g‐ENaC mRNA level (p=0.04) was observed in comparison to normotensive arteries. In aortas, there was a significant increase in a‐ENaC mRNA level (p=0.006) in hypertension but no change in b‐ and g‐ENaC expression. In mesenteric arteries, spiro‐treatment decreased a‐ENaC and g‐ENaC in comparison to hypertensive controls. In aortas, a‐ENaC mRNA level was significantly decreased (p=0.002) by spiro‐treatment compared to hypertensive controls. In summary, we observed an upregulation of vascular ENaC mRNA in arteries during hypertension and found that antihypertensive treatment with spironolactone decreased this upregulation. This data suggests a strong link between pathogenesis of hypertension and vascular ENaC expression. Support or Funding Information University of Otago Doctoral Scholarship, Department of Physiology, Otago Medical Research Foundation, Lottery Grants Board This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .