Dietary NaCl loading enhances antihypertensive effect of guanabenz in spontaneously hypertensive rats.
Our previous studies demonstrated that high dietary NaCl intake causes increases in blood pressure and plasma norepinephrine (NE) levels and a decrease in NE release associated with local upregulation of alpha 2-adrenoceptor number in the anterior hypothalamic area (AHA) of NaCl-sensitive spontaneously hypertensive rats (SHR-S). Further, acute microinjection of clonidine into the AHA of SHR-S fed a high NaCl diet resulted in greater depressor and bradycardic responses than in SHR-S receiving a normal NaCl diet. The current study tested the hypothesis that the antihypertensive effect of chronic systemic administration of guanabenz (0.24 micrograms/kg/min, IV) is enhanced in SHR-S maintained on a high (8%) NaCl diet than in control rats on a normal (1% NaCl) diet. After two weeks on the diets, mean arterial pressure (MAP) and heart rate (HR) were measured and blood for NE and epinephrine (E) assay was collected from intra-arterial cannulas in conscious, unrestrained rats. The ratio of left ventricle and septum to body weight (LV + S/BW) was determined. Chronic infusion of guanabenz significantly decreased MAP (P less than .05), HR (P less than .01) and LV + S/BW (P less than .01) in 8% NaCl fed SHR-S, but not in 1% NaCl fed SHR-S (P greater than .1). Guanabenz tended to reduce plasma NE levels in 8% NaCl fed SHR-S (.1 greater than P greater than .05), but not in 1% NaCl fed rats (P greater than .1).(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medicine, University of Alabama, Birmingham 35294.
H K
HK
Jin
R H
RH
Yang
Y F
YF
Chen
J M
JM
Wyss
S
S
Oparil
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004032:Diet; D004357:Drug Synergism; D006143:Guanabenz / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D012965:Sodium Chloride / Q000494:pharmacology*
D000959:Antihypertensive Agents; D006146:Guanidines; D012965:Sodium Chloride; D006143:Guanabenz