Acid-Sensing Ion Channel 1a Deficiency Drives Endocrine Hypertension in Male Mice

Area of Science:

• Cardiovascular Physiology
• Endocrinology
• Ion Channel Biology

Background:

• Acid-sensing ion channel 1a (ASIC1a) is an H+-gated cation channel involved in various physiological and pathological states.
• ASIC1a's role in blood pressure regulation, particularly concerning sex, aging, and disease, remains largely unclear.
• Understanding ASIC1a's function is crucial for elucidating mechanisms of hypertension.

Purpose of the Study:

• To investigate the sex-specific contribution of ASIC1a to cardiovascular function.
• To determine ASIC1a's role in cardiovascular homeostasis during aging.
• To assess ASIC1a's modulation of angiotensin II-induced systemic hypertension.

Main Methods:

• Radiotelemetry implantation in male and female wild-type and ASIC1a knockout mice of different ages (6 and 18 months).
• Monitoring of mean arterial blood pressure and heart rate under baseline and angiotensin II-infused conditions.
• Assessment of blood gases, electrolytes, hormones, and end-organ injury.

Main Results:

• Aged male ASIC1a knockout mice developed hypertension, characterized by aldosterone excess, sympathetic overactivity, cardiac hypertrophy, and aortic/glomerular fibrosis.
• Female ASIC1a knockout mice showed no significant cardiovascular changes.
• In male knockout mice, hyperaldosteronism occurred independently of the renin-angiotensin system and attenuated angiotensin II-induced hypertension; early corticosterone excess was observed in younger males.

Conclusions:

• ASIC1a acts as a novel, sex-specific regulator of cardiovascular function.
• ASIC1a deficiency is linked to early corticosterone excess and hyperaldosteronism in males, potentially driving endocrine-related hypertension.
• These findings highlight ASIC1a's critical role in sex-specific blood pressure control and hypertension development.