Abstract :
A complete atrial natriuretic factor (ANF) synthetic, processing, and effector system is found in rat brain and expressed at particularly high levels in brain regions involved in cardiovascular and volume regulation, including the anterior hypothalamic area and nucleus tractus solitarius (NTS). Studies employing microinjection of a blocking monoclonal antibody to ANF demonstrated for the first time that endogenous ANF in the brain is functionally active in the tonic control of blood pressure and baroreflex sensitivity in the SHR but plays a lesser role in the normotensive WKY control. In the WKY, excitation of NTS neurons by baroreflex afferents leads to activation of sympathoinhibitory neurons in NTS and anterior hypothalamic area, strong inhibition of sympathetic nervous system outflow, and a decrease in arterial pressure. In SHR, brain ANF acts at the levels of the NTS and the anterior hypothalamus to perturb this baroreflex regulatory pathway. ANF tonically activates sympathoinhibitory neurons in the caudal NTS of SHR, thereby restraining the rise in arterial pressure, and tonically inhibits baroreflex responsiveness to alterations in blood pressure. Attenuated baroreflex-mediated input to the anterior hypothalamic area, in combination with inhibition of norepinephrine release from anterior hypothalamic nerve terminals by locally active ANF, reduces activation of sympathoinhibitory neurons in the anterior hypothalamic area. This, in turn, results in increased sympathetic outflow and higher blood pressure in the SHR. Thus ANF appears to act at a number of sites in brain to facilitate the development and maintenance of sympathetically mediated hypertension in the SHR model.
