Alpha2A-adrenergic receptors mediate sympathoinhibitory responses to atrial natriuretic peptide in the mouse anterior hypothalamic nucleus.
In the rat, activation of alpha2-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 alpha2-adrenergic receptors, and thereby contributes to NaCl-sensitive hypertension in spontaneously hypertensive rats. To further test the specificity of this mechanism, either alpha2-adrenergic receptor agonists or atrial natriuretic peptide was microinjected into anterior hypothalamic nucleus of conscious C57BL/6 mice in which the alpha2-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) alpha2A-adrenergic receptors mediate both sympathoinhibitory responses to alpha2-adrenergic receptor agonists and the action of atrial natriuretic peptide.
Peng
Ning
N
Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294-0006, USA.
Chambless
Brandon D
BD
Oparil
Suzanne
S
Wyss
J Michael
JM
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D007025:Anterior Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology*; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D006143:Guanabenz / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009433:Neural Inhibition; D017354:Point Mutation; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology*
C547769:Adra2a protein, mouse; C547770:Adra2a protein, rat; D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D018341:Receptors, Adrenergic, alpha-2; D009320:Atrial Natriuretic Factor; D006143:Guanabenz; D003000:Clonidine