The neural basis of salt sensitivity in the rat: altered hypothalamic function.
Dietary NaCl supplementation in NaCl-sensitive spontaneously hypertensive rats (SHR-S) elevates blood pressure, increases peripheral sympathetic nervous system activity and depresses endogenous noradrenaline stores and noradrenaline release in the anterior hypothalamus. NaCl-resistant spontaneously hypertensive rats (SHR-R) and normotensive Wistar Kyoto (WKY) rats are resistant to the NaCl-induced alterations in blood pressure and central and peripheral noradrenergic activity, suggesting that the alterations observed in the SHR-S during NaCl loading are genetically mediated. The anterior hypothalamus is a major cardiovascular regulatory region, and depressor responses elicited by pharmacologic (alpha 2 adrenoceptor) stimulation of this area are exaggerated in SHR-S fed a high NaCl diet compared with SHR-S fed a basal diet and compared with SHR-R and WKY fed a high or basal NaCl diet. Membrane-binding techniques confirm that alpha 2 adrenoceptors in the anterior hypothalamic area are increased in number in SHR-S fed a high NaCl diet, presumably reflecting upregulation in response to reduced local noradrenaline release. These findings are consistent with the hypothesis that decreased noradrenergic activity of sympathoinhibitory neurons in the anterior hypothalamic area may mediate the exacerbation in hypertension that occurs in SHR-S during dietary NaCl supplementation.
Oparil
S
S
Department of Medicine, University of Alabama, Birmingham 35294.
Chen
Y F
YF
Meng
Q C
QC
Yang
R H
RH
Jin
H K
HK
Wyss
J M
JM
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology; D004195:Disease Models, Animal; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D007032:Hypothalamus, Anterior / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D012982:Sodium, Dietary / Q000008:administration & dosage / Q000494:pharmacology*
D011942:Receptors, Adrenergic, alpha; D012982:Sodium, Dietary; D003000:Clonidine