Selenium deficiency causes hypertension by increasing renal AT1 receptor expression via GPx1/H2O2/NF-κB pathway.

Epidemiological studies show an association between low body selenium and the risk of hypertension. However, whether selenium deficiency causes hypertension remains unknown. Here, we report that Sprague-Dawley rats fed a selenium-deficient diet for 16 weeks developed hypertension, accompanied with decreased sodium excretion. The hypertension of selenium-deficient rats was associated with increased renal angiotensin II type 1 receptor (AT 1 R) expression and function that was reflected by the increase in sodium excretion after the intrarenal infusion of the AT 1 R antagonist candesartan. Selenium-deficient rats had increased systemic and renal oxidative stress; treatment with the antioxidant tempol for 4 weeks decreased the elevated blood pressure, increased sodium excretion, and normalized renal AT 1 R expression. Among the altered selenoproteins in selenium-deficient rats, the decrease in renal glutathione peroxidase 1 (GPx1) expression was most prominent. GPx1, via regulation of NF-κB p65 expression and activity, was involved in the regulation of renal AT 1 R expression because treatment with dithiocarbamate (PDTC), an NF-κB inhibitor, reversed the up-regulation of AT 1 R expression in selenium-deficient renal proximal tubule (RPT) cells. The up-regulation of AT 1 R expression with GPx1 silencing was restored by PDTC. Moreover, treatment with ebselen, a GPX1 mimic, reduced the increased renal AT 1 R expression, Na+-K+-ATPase activity, hydrogen peroxide (H 2 O 2) generation, and the nuclear translocation of NF-κB p65 protein in selenium-deficient RPT cells. Our results demonstrated that long-term selenium deficiency causes hypertension, which is due, at least in part, to decreased urine sodium excretion. Selenium deficiency increases H 2 O 2 production by reducing GPx1 expression, which enhances NF-κB activity, increases renal AT 1 R expression, causes sodium retention and consequently increases blood pressure. [Display omitted] • Long-term selenium deficiency causes hypertension. • Selenium deficiency increases renal AT 1 R expression and sodium retention. • Selenium deficiency elevates NF-κB activity via GPx1/H 2 O 2 pathway. [ABSTRACT FROM AUTHOR]