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1 Hypertension Unit, University of Ottawa Heart Institute, Ottawa, ON, Canada
* To whom correspondence should be addressed. E-mail: fleenen{at}ottawaheart.ca.
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 ouabain-like compounds (OLC), and thereby sympathetic hyperactivity and hypertension. In conscious Wistar rats, intracerebroventricular (icv) infusion of aldosterone at 300 or 900 ng/h in 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). Icv infusion of aCSF containing 0.16 M Na+ (vs 0.145 M Na+ in regular aCSF) did not change MAP or RSNA, but after icv infusion of aldosterone at 300 ng/h for 2 h caused significant increases in MAP, RSNA, and HR. Icv infusion of aCSF containing 0.3 M Na+ increased MAP, RSNA, and HR significantly more after icv infusion of aldosterone vs vehicle. After icv infusion of aldosterone, the MAP, RSNA, and HR responses to icv infusion of aCSF containing 0.16 M Na+ were blocked by blockade of brain OLC with icv Fab fragments or of brain sodium channels with icv benzamil. Chronic icv infusion of aldosterone at 25 ng/h in aCSF with 0.15 M Na+ for 2 weeks increased MAP by 15-20 mmHg, 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 CSFNa+ leading to increases in brain OLC, sympathetic outflow and blood pressure.
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