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Brain sodium channels and ouabainlike compounds mediate central aldosterone-induced hypertension

Hypertension Unit, University of Ottawa Heart Institute, Ottawa, Ontario, Canada K1Y 4W7

Submitted 12 August 2003 ; accepted in final form 12 August 2003

Central nervous system (CNS) effects of mineralocorticoids participate in the development of salt-sensitive hypertension. In the brain, mineralocorticoids activate amiloride-sensitive sodium channels, and we hypothesized that this would lead to increased release of ouabainlike compounds (OLC) and thereby sympathetic hyperactivity and hypertension. In conscious Wistar rats, intracerebroventricular infusion of aldosterone at 300 or 900 ng/h in artificial cerebrospinal fluid (aCSF) with 0.145 M Na⁺ for 2 h did not change baseline mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), or heart rate (HR). Intracerebroventricular infusion of aCSF containing 0.16 M Na⁺ (versus 0.145 M Na⁺ in regular aCSF) did not change MAP or RSNA, but significant increases in MAP, RSNA, and HR were observed after intracerebroventricular infusion of aldosterone at 300 ng/h for 2 h. Intracerebroventricular infusion of aCSF containing 0.3 M Na⁺ increased MAP, RSNA, and HR significantly more after intracerebroventricular infusion of aldosterone versus vehicle. After intracerebroventricular infusion of aldosterone, the MAP, RSNA, and HR responses to intracerebroventricular infusion of aCSF containing 0.16 M Na⁺ were blocked by blockade of brain OLC with intracerebroventricular infusion of Fab fragments or of brain sodium channels with intracerebroventricular benzamil. Chronic intracerebroventricular infusion of aldosterone at 25 ng/h in aCSF with 0.15 M Na⁺ for 2 wk increased MAP by 15–20 mmHg and increased hypothalamic OLC by 30% and pituitary OLC by 60%. Benzamil blocked all these responses to aldosterone. These findings indicate that in the brain, mineralocorticoids activate brain sodium channels, with small increases in CSF Na⁺ leading to increases in brain OLC, sympathetic outflow, and blood pressure.

benzamil; blood pressure

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