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(Hypertension. 2003;41:571.)
© 2003 American Heart Association, Inc.

Scientific Contributions

_2A-Adrenergic Receptors Mediate Sympathoinhibitory Responses to Atrial Natriuretic Peptide in the Mouse Anterior Hypothalamic Nucleus

From the Department of Cell Biology (N.P., B.D.C., J.M.W.) and the Vascular Biology and Hypertension Program of the Department of Medicine (S.O., J.M.W.), University of Alabama at Birmingham.

Correspondence to J. Michael Wyss, PhD, Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294-0006. E-mail jmwyss{at}uab.edu

In the rat, activation of ₂-adrenergic receptors in the anterior hypothalamic nucleus inhibits sympathetic nervous system activity. Furthermore, local release of atrial natriuretic peptide inhibits norepinephrine release in this nucleus, blocking local activation of ₂-adrenergic receptors, and thereby contributes to NaCl-sensitive hypertension in spontaneously hypertensive rats. To further test the specificity of this mechanism, either ₂-adrenergic receptor agonists or atrial natriuretic peptide was microinjected into anterior hypothalamic nucleus of conscious C57BL/6 mice in which the ₂-adrenergic receptor was functionally deleted by a single point mutation (n=10 per group). In control mice, microinjection of either clonidine or guanabenz (10^-3 to 10^-7 mol/L) caused a rapid fall in mean arterial pressure that lasted for several minutes. In the knockout mice there was no response to the injection of either dose of either agonist. Microinjection of atrial natriuretic peptide (10^-6 to 10^-7 mol/L) caused a rapid increase in mean arterial pressure (8.2±1.3 and 6.55±1.2 mm Hg, respectively) in the control mice that was similar to the responses previously observed in Wistar-Kyoto rats. In contrast, the microinjections did not significantly alter mean arterial pressure in the knockout mice. These experiments demonstrate that in the anterior hypothalamic nucleus of the mouse (and probably in the rat) _2A-adrenergic receptors mediate both sympathoinhibitory responses to ₂-adrenergic receptor agonists and the action of atrial natriuretic peptide.

Key Words: hypertension, experimental • hypothalamus • receptors, adrenergic • norepinephrine • rats