ANTERIOR HYPOTHALAMIC NOREPINEPHRINE, ATRIAL-NATRIURETIC-PEPTIDE, ANDHYPERTENSION

Our laboratory has characterized a model of salt sensitive hypertensio n, the salt sensitive spontaneously hypertensive rat (SHR-S), in which dietary NaCl supplementation increases blood pressure by reducing nor epinephrine release by nerve terminals in the anterior hypothalamic ar ea (AHA), thus reducing activation of sympathoinhibitory neurons in th e AHA. This, in turn, results in increased sympathetic outflow and hig her blood pressure in the SHR. Two mechanisms have been shown to contr ibute to this effect: (i) reduced noradrenergic input into AHA via bar oreflex pathways and (ii) local inhibition of NE release in AHA by the inhibitory neuromodulator atrial natriuretic peptide (ANP). Studies e mploying microinjection of a blocking monoclonal antibody to ANP direc tly into the AHA and the nucleus tractus solitarius (NTS) demonstrated for the first time that endogenous ANP in the brain is functionally a ctive in the tonic control of blood pressure and baroreflex sensitivit y in the SHR-S but plays a lesser role in the normotensive Wistar Kyot o (WKY) control. In the WKY, excitation of NTS neurons by baroreflex a fferents leads to activation of sympathoinhibitory neurons in NTS and AHA, strong inhibition of sympathetic nervous system outflow, and a de crease in arterial pressure. In SHR-S, brain ANP acts at the levels of the NTS and the AHA to perturb this baroreflex regulatory pathway. AN P tonically activates sympathoinhibitory neurons in the caudal NTS of SHR-S, thereby restraining the rise in arterial pressure, and tonicall y inhibits baroreflex responsiveness to alterations in blood pressure. Thus ANP appears to act at a number of sites in brain to facilitate t he development and maintenance of sympathetically mediated hypertensio n in the SHR-S model. (C) 1996 Academic Press, Inc.