11β-Hydroxysteroid Dehydrogenase Type 2 Activity in Hypothalamic Paraventricular Nucleus Modulates Sympathetic Excitation

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Abstract
Aldosterone stimulates the sympathetic nervous system by binding to a select population of brain mineralocorticoid receptors (MR). These MR have an equal affinity for corticosterone that is present in substantially higher concentrations, but are held in reserve for aldosterone by activity of the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD-2), which converts corticosterone to an inactive metabolite. Thus, colocalization of MR and 11β-HSD-2 activity may help identify brain regions that mediate the effects of aldosterone. The present studies tested the hypothesis that 11β-HSD-2 activity regulates MR-mediated responses in the paraventricular nucleus (PVN) of the hypothalamus, a forebrain region implicated in sympathetic regulation. Real-time–polymerase chain reaction revealed the presence of 11β-HSD-2 mRNA in PVN. In anesthetized adult male Sprague-Dawley rats, microinjection of the 11β-HSD-2 inhibitor carbenoxolone (CBX) into PVN increased mean arterial pressure, heart rate, and renal sympathetic...