Electrolyte and transporter responses to angiotensin II induced hypertension in female and male rats and mice

Aim Sexual dimorphisms are evident along the nephron: Females (F) exhibit higher ratios of renal distal to proximal Na + transporters' abundance, greater lithium clearance (C Li ) more rapid natriuresis in response to saline infusion and lower plasma [K + ] vs. males (M). During angiotensin II infusion hypertension (AngII‐HTN) M exhibit distal Na + transporter activation, lower proximal and medullary loop transporters, blunted natriuresis in response to saline load, and reduced plasma [K + ]. This study aimed to determine whether responses of F to AngII‐HTN mimicked those in M or were impacted by sexual dimorphisms evident at baseline. Methods Sprague Dawley rats and C57BL/6 mice were AngII infused via osmotic minipumps 2 and 3 weeks, respectively, and assessed by metabolic cage collections, tail‐cuff sphygmomanometer, semi‐quantitative immunoblotting of kidney and patch‐clamp electrophysiology. Results In F rats, AngII‐infusion increased BP to 190 mm Hg, increased phosphorylation of cortical NKCC2, NCC and cleavage of ENaC two to threefold, increased ENaC channel activity threefold and aldosterone 10‐fold. K + excretion increased and plasma [K + ] decreased. Evidence of natriuresis in F included increased urine Na + excretion and C Li , and decreased medullary NHE3, NKCC2 and Na,K‐ATPase abundance. In C57BL/6 mice, AngII‐HTN increased abundance of distal Na + transporters, suppressed proximal‐medullary transporters and reduced plasma [K + ] in both F and M. Conclusion Despite baseline sexual dimorphisms, AngII‐HTN provokes similar increases in BP, aldosterone, distal transporters, ENaC channel activation and K + loss accompanied by similar suppression of proximal and loop Na + transporters, natriuresis and diuresis in females and males.