Role of collecting duct principal cell NOS1β in sodium and potassium homeostasis

Academic Article


  • The nitric oxide (NO)-generating enzyme, NO synthase-1β (NOS1β), is essential for sodium (Na+) homeostasis and blood pressure control. We previously showed that collecting duct principal cell NOS1β is critical for inhibition of the epithelial sodium channel (ENaC) during high Na+ intake. Previous studies on freshly isolated cortical collecting ducts (CCD) demonstrated that exogenous NO promotes basolateral potassium (K+) conductance through basolateral channels, presumably Kir4.1 (Kcnj10) and Kir5.1 (Kcnj16). We, therefore, investigated the effects of NOS1β knockout on Kir4.1/Kir5.1 channel activity. Indeed, in CHO cells overexpressing NOS1β and Kir4.1/Kir5.1, the inhibition of NO signaling decreased channel activity. Male littermate control and principal cell NOS1β knockout mice (CDNOS1KO) on a 7-day, 4% NaCl diet (HSD) were used to detect changes in basolateral K+ conductance. We previously demonstrated that CDNOS1KO mice have high circulating aldosterone despite a high-salt diet and appropriately suppressed renin. We observed greater Kir4.1 cortical abundance and significantly greater Kir4.1/Kir5.1 single-channel activity in the principal cells from CDNOS1KO mice. Moreover, blocking aldosterone action with in vivo spironolactone treatment resulted in lower Kir4.1 abundance and greater plasma K+ in the CDNOS1KO mice compared to controls. Lowering K+ content in the HSD prevented the high aldosterone and greater plasma Na+ of CDNOS1KO mice and normalized Kir4.1 abundance. We conclude that during chronic HSD, lack of NOS1β leads to increased plasma K+, enhanced circulating aldosterone, and activation of ENaC and Kir4.1/Kir5.1 channels. Thus, principal cell NOS1β is required for the regulation of both Na+ and K+ by the kidney.
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    Author List

  • Hyndman KA; Isaeva E; Palygin O; Mendoza LD; Rodan AR; Staruschenko A; Pollock JS
  • Volume

  • 9
  • Issue

  • 20