Intrahypothalamic clonidine infusion prevents NaCl-sensitive hypertension.
We have previously shown that dietary NaCl supplementation increases blood pressure and sympathetic nervous system activity in association with decreased norepinephrine release and increased alpha 2-adrenergic receptor number in the anterior hypothalamic area of salt-sensitive spontaneously hypertensive rats (SHR-S) but not in salt-resistant spontaneously hypertensive rats (SHR-R) or Wistar-Kyoto (WKY) rats. Further, acute microinjection of clonidine into the anterior hypothalamic area produced depressor responses that were augmented by high salt feeding in SHR-S but not in SHR-R or WKY rats. The current study tested the hypothesis that chronic infusion of clonidine into the anterior hypothalamic area prevents salt-sensitive hypertension in SHR-S. Beginning at age 7 weeks, immediately before initiation of 1% or 8% salt diets, clonidine (2 ng/min) or saline vehicle was infused into the anterior hypothalamic area or femoral vein of male SHR-S via osmotic minipump for 20 days. In SHR-S fed an 8% salt diet, chronic microinfusion of clonidine into the anterior hypothalamic area offset the hypertensive effect of the dietary salt supplementation and reduced the enhancing effects of dietary salt on left ventricular weight and plasma norepinephrine levels. In contrast, chronic microinfusion of clonidine into the anterior hypothalamic area did not significantly affect any of these measures in 1% salt-fed SHR-S. Intravenous infusion of clonidine at the rate used for the anterior hypothalamic area infusion did not alter any of these measures in 8% salt-fed SHR-S.(ABSTRACT TRUNCATED AT 250 WORDS)
Jin
H K
HK
Department of Medicine, University of Alabama, Birmingham 35294.
Yang
R H
RH
Wyss
J M
JM
Chen
Y F
YF
Oparil
S
S
D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000033:anatomy & histology; D006973:Hypertension / Q000139:chemically induced / Q000517:prevention & control*; D007031:Hypothalamus / Q000187:drug effects*; D007263:Infusions, Parenteral; D008297:Male; D009638:Norepinephrine / Q000097:blood; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D012982:Sodium, Dietary / Q000009:adverse effects*
D012982:Sodium, Dietary; D003000:Clonidine; D009638:Norepinephrine