[Effect of beta3-adrenoceptor antagonist on the cardiac function and expression of endothelial nitric oxide synthase in a rat model of heart failure].
OBJECTIVE
To investigate the effect of beta(3)-adrenoceptor (beta(3)-AR) antagonist (SR59230A) on the cardiac function and left ventricular remodeling in a rat model of heart failure induced by isoproterenol (ISO), and to probe into its mechanism.


METHODS
Eight rats were randomly selected to serve as controls from 85 male adult Wistar rats. After a heart failure model was reproduced, twenty remain rats were randomly divided into ISO group (n = 10) and SR59230A group (SR group, n = 10). ISO group received intraperitoneal injection of 1 ml saline twice a day; SR group received intraperitoneal injection of 85 nmol SR59230A in 1 ml saline twice a day; control group received no treatment. The parameters determined included echocardiogram, the expression of nitric oxide synthase (eNOS) of left ventricle by the technique of reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, cyclic guanosine monophosphate (cGMP) level by enzyme linked immunosorbent assay (ELISA), the ratio of left ventricular weight and body weight (LVW/BW), and the ratio of lung weight and body weight (PW/BW).


RESULTS
Compared with control group, the left ventricular end systolic pressure (LVESP), the maximum and minimum first derivative of left ventricular pressure (+/-dp/dtmax) were significantly decreased (all P<0.01), while heart rate (HR) and left ventricular end-diastolic pressure (LVEDP) were significantly increased (both P<0.01) in ISO group. Compared with ISO group, LVESP, +/-dp/dtmax were markedly higher (P<0.05 or P<0.01) respectively, whereas HR and LVEDP were markedly lower (P<0.05 and P<0.01) in SR group, and there was no difference in HR between SR group and control group (P>0.05), while LVEDP was higher in RS group than control group (P<0.01). The levels of eNOS mRNA, protein and cGMP were significantly lower in SR group compared with ISO group (all P<0.01). In addition, when compared with ISO group, LVW/BW ratio and PW/BW ratio in SR group were also decreased (both P<0.05).


CONCLUSIONS
beta(3)-AR antagonist SR59230A can block the beta(3)-AR-NOS-cGMP pathway and improve cardiac function in heart failure in rat when if is administered for a long term. SR59230A can also improve left ventricular remodeling in a certain degree.
Gan
Run-tao
RT
Department of Cardiology, The First Clinical College of Harbin Medical University, Harbin 150001, Heilongjiang, China. ganrt@126.com
Li
Wei-min
WM
Wang
Xu
X
Wu
Shuang
S
Kong
Yi-hui
YH
D058673:Adrenergic beta-3 Receptor Antagonists; D000818:Animals; D004195:Disease Models, Animal; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D011412:Propanolamines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D016277:Ventricular Function, Left / Q000187:drug effects*; D020257:Ventricular Remodeling / Q000187:drug effects
C097869:3-(2-ethylphenoxy)-1-(1,2,3,4-tetrahydronaphth-1-ylamino)-2-propanol oxalate; D058673:Adrenergic beta-3 Receptor Antagonists; D011412:Propanolamines; D012333:RNA, Messenger; D052250:Nitric Oxide Synthase Type III