Antihypertensive effect of cicletanine is exaggerated in NaCl-sensitive hypertension.
Cicletanine (CIC), a furopyridine derivative, lowers blood pressure in hypertensive animals and humans. We have previously identified an NaCl-sensitive substrain of spontaneously hypertensive rat (SHR-S) that displays enhanced sensitivity to the depressor effects of exogenous atrial natriuretic peptide (ANP) when fed a high NaCl diet. The current study tested the hypotheses that CIC has an exaggerated antihypertensive effect in NaCl-supplemented SHR-S and that this effect might be ANP dependent. CIC (40 mg/kg/day) or vehicle was administered by gavage in a single daily dose for three weeks beginning immediately prior to initiation of 1% or 8% NaCl diets in seven-week-old male SHR-S. CIC significantly decreased mean arterial pressure (MAP) and the ratio of left ventricular and septum weight to body weight (LV + S/BW) in both 8% NaCl- and 1% NaCl-fed SHR-S. The depressor effect of CIC was greater in the 8% NaCl group (-26 mmHg) than in the 1% NaCl group (-13 mmHg). CIC was associated with significant reduction in RAP in the 8% NaCl group but not in the 1% NaCl group. Neither CIC treatment nor 8% NaCl significantly altered plasma ANP or cyclic guanosine monophosphate (GMP) levels in plasma, aorta, or kidney. CIC was associated with significant decreases in plasma norepinephrine (NE) levels in the 1% NaCl group but not in the 8% NaCl group. The data demonstrate that the antihypertensive effect of CIC is exaggerated in NaCl-sensitive hypertension. The antihypertensive effect of CIC appears not to be related to ANP or cyclic GMP but may be related to a combination of a sympatholytic and natriuretic/diuretic effects in SHR-S.
Jin
H K
HK
Department of Medicine, University of Alabama, Birmingham 35294.
Yang
R H
RH
Esunge
P
P
Chen
Y F
YF
Durand
J
J
Oparil
S
S
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D009320:Atrial Natriuretic Factor / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism; D004232:Diuretics / Q000627:therapeutic use*; D004837:Epinephrine / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D011725:Pyridines; D051381:Rats; D011918:Rats, Inbred SHR; D012965:Sodium Chloride / Q000494:pharmacology*; D012982:Sodium, Dietary / Q000494:pharmacology*
D000959:Antihypertensive Agents; D004232:Diuretics; D011725:Pyridines; D012982:Sodium, Dietary; D012965:Sodium Chloride; D009320:Atrial Natriuretic Factor; C038068:cicletanine; D006152:Cyclic GMP; D004837:Epinephrine