Acid‐sensing ion channel 1a deficiency drives endocrine hypertension in male mice

mice exhibit elevated corticosterone, hypokalaemia, reduced urine osmolality, increased pulse pressure and cardiomyocyte hypertrophy. Together, these findings identify ASIC1a as a novel, sex-specific regulator of cardiovascular function, suggesting that ASIC1a deficiency may be a potential driver of endocrine-related hypertension. KEY POINTS: Extracellular acidosis, which occurs during pathological conditions such as ischaemia, inflammation and metabolic stress, contributes to the pathogenesis of cardiometabolic disease. Acid-sensing ion channels (ASICs) are key sensors of acidosis and important mediators of endothelium-dependent vasodilatation; however, the role of ASIC1a in blood pressure regulation remains poorly understood. Here we report that ASIC1a deficiency causes hypertension in aged male mice that is driven by an excess of aldosterone and increased sympathetic activity, while female mice remain unaffected. Hyperaldosteronism occurs independently of angiotensin II but is associated with elevated corticosterone that precedes the development of hypertension. We further show that male, but not female, ASIC1a knockout mice have a reduced sensitivity to angiotensin II-induced hypertension. These findings identify ASIC1a as a novel, sex-specific regulator of cardiovascular function, suggesting that ASIC1a deficiency contributes to endocrine-related hypertension.