Anterior hypothalamic norepinephrine, atrial natriuretic peptide, and hypertension.
Our laboratory has characterized a model of salt sensitive hypertension, the salt sensitive spontaneously hypertensive rat (SHR-S), in which dietary NaCl supplementation increases blood pressure by reducing norepinephrine release by nerve terminals in the anterior hypothalamic area (AHA), thus reducing activation of sympathoinhibitory neurons in the AHA. This, in turn, results in increased sympathetic outflow and higher blood pressure in the SHR. Two mechanisms have been shown to contribute to this effect: (i) reduced noradrenergic input into AHA via baroreflex pathways and (ii) local inhibition of NE release in AHA by the inhibitory neuromodulator atrial natriuretic peptide (ANP). Studies employing microinjection of a blocking monoclonal antibody to ANP directly into the AHA and the nucleus tractus solitarius (NTS) demonstrated for the first time that endogenous ANP in the brain is functionally active in the tonic control of blood pressure and baroreflex sensitivity in the SHR-S but plays a lesser role in the normotensive Wistar Kyoto (WKY) control. In the WKY, excitation of NTS neurons by baroreflex afferents leads to activation of sympathoinhibitory neurons in NTS and AHA, strong inhibition of sympathetic nervous system outflow, and a decrease in arterial pressure. In SHR-S, brain ANP acts at the levels of the NTS and the AHA to perturb this baroreflex regulatory pathway. ANP tonically activates sympathoinhibitory neurons in the caudal NTS of SHR-S, thereby restraining the rise in arterial pressure, and tonically inhibits baroreflex responsiveness to alterations in blood pressure. Thus ANP appears to act at a number of sites in brain to facilitate the development and maintenance of sympathetically mediated hypertension in the SHR-S model.
Oparil
S
S
Department of Medicine, University of Alabama at Birmingham 35294-0019, USA.
Chen
Y F
YF
Peng
N
N
Wyss
J M
JM
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D007032:Hypothalamus, Anterior / Q000378:metabolism* / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism* / Q000502:physiology; D051381:Rats
D009320:Atrial Natriuretic Factor; D009638:Norepinephrine