Year: 2025
Type: article
Abstract: ABSTRACT Background Acid-sensing ion channel 1a (ASIC1a) is an H + -gated cation channel that responds to extracellular acidosis in both normal and pathological states, including ischemia, inflammation, and metabolic disturbances. While ASIC1a regulates vascular reactivity, its role in blood pressure regulation remains unclear, particularly concerning sex, aging, and disease. This study aims to investigate whether ASIC1a: 1) contributes to cardiovascular function in a sex-dependent manner; 2) plays a dynamic role in cardiovascular homeostasis with aging; and 3) modulates the development of angiotensin II-induced systemic hypertension. Methods Radiotelemeters were implanted in 6- and 18-month-old male and female wild-type ( Asic1a +/+ ) and ASIC1a knockout ( Asic1a -/- ) mice to monitor mean arterial blood pressure and heart rate under baseline conditions and in response to angiotensin II. Blood gases, electrolytes, hormones, and end-organ injury were also assessed. Results Aged male Asic1a -/- mice develop hypertension driven by aldosterone excess and sympathetic overactivity, which is accompanied by cardiac hypertrophy, aortic fibrosis, and glomerular hypertrophy. Female Asic1a -/- mice remain unaffected. In male Asic1a -/- mice, hyperaldosteronism occurs independent of the renin-angiotensin system and mitigates angiotensin II-induced hypertension. Furthermore, 6-month-old male Asic1a -/- mice exhibit elevated corticosterone, hypokalemia, reduced urine osmolality, increased pulse pressure, and cardiomyocyte hypertrophy that precedes hypertension. Conclusions These findings establish ASIC1a as a novel, sex-specific regulator of cardiovascular function, linking early corticosterone excess in male mice to hyperaldosteronism and implicating ASIC1a deficiency as a potential driver of endocrine-related hypertension. GRAPHICAL ABSTRACT
Source: The Journal of Physiology
DOI: 10.1113/jp289258
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,400
Awards: G1325005805, Metabolic Dysfunction in Pulmonary Hypertension, Vascular Smooth Muscle Function in Pulmonary Hypertension, Contributions of altered subcellular localization of acid-sensing ion channel 1a to pulmonary hypertension, G2572323177, G3992294412, G399504500, G4842716684, G4955992801, G6638343088, G6702114788, Academic Science Education and Research Training, The Role of Mitochondrial Acid-Sensing Ion Channel 1 in Pulmonary Hypertension, Initiative to Maximize Student Diversity at the University of New Mexico Health Sciences Center 2021, Minority Institutional Research Training Program (T32), Oxidant Signaling in Pulmonary Hypertension, G962487624, The Role of the Acid Sensing Io Channel 1 in the Systemic Vasculature
OpenAlex ID: W4416247793