TASK-3 CHANNEL DELETION IN MICE RECAPITUATES LOW RENIN ESSENTIAL HYPERTENSION

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 59; no. 5; pp. 999 - 1005
• Main Authors: Guagliardo, Nick A, Yao, Junlan, Hu, Changlong, Schertz, Elaine M, Tyson, David A, Carey, Robert M, Bayliss, Douglas A, Barrett, Paula Q
• Format: Journal Article
• Language: English
• Published: 09.04.2012
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/HYPERTENSIONAHA.111.189662

Idiopathic primary hyperaldosteronism (IHA) and low-renin essential hypertension (LREH) are common forms of hypertension, characterized by an elevated aldosterone-renin ratio (ARR) and hypersensitivity to Angiotensin II (Ang II). They are suggested to be two states within a disease spectrum that progresses from LREH to IHA as the control of aldosterone production by the renin-angiotensin system is weakened. The mechanism(s) that drive this progression remain unknown. Deletion of Twik-related-acid-sensitive K + channels (TASK) subunits, TASK-1 and TASK-3, in mice (T1T3KO) produces a model of human IHA. Here, we determine the effect of deleting only TASK-3 on the control of aldosterone production and blood pressure. We find that T3KO mice recapitulate key characteristics of human LREH: salt-sensitive hypertension, mild overproduction of aldosterone, decreased plasma renin concentration with elevated ARR, hypersensitivity to endogenous and exogenous Ang II, and failure to suppress aldosterone production with dietary sodium loading. The relative differences in levels of aldosterone output and ARR, and in autonomy of aldosterone production between T1T3KO and T3KO mice are reminiscent of differences in human hypertensive patients with LREH and IHA. Our studies establish a model of LREH and suggest that loss of TASK channel activity may be one mechanism that advances the syndrome of low renin hypertension.