[Effect of beta3-adrenoreceptors agonist on beta3-adrenoreceptors expression and myocyte apoptosis in a rat model of heart failure].
OBJECTIVE
To evaluate the effects of beta(3)-adrenoreceptor (AR) agonist (BRL-37344) on the expression of beta(3)-AR in a isoproterenol (ISO)-induced heart failure (HF) rat model and to investigate the influence on the levels of beta(3)-AR in failing heart.


METHODS
The rats were randomly divided into four groups: I group (control group, n=10); II group (normal with BRL group, n=10); III group (HF group, n=30); IV group (HF with BRL group, n=35).II and IV groups received BRL 0.4 nmol.kg-1.min-1 through caudal vein for 10 minutes twice a week. I and III groups received saline at the same time. The measure included hemodynamics, the expression of beta3-AR in left ventricular myocytes by the techniques of immunohistochemistry, beta3-AR proteins by western blot, expression levels of beta3-AR mRNA in myocardium by reverse transcription- polymerase chain reaction (RT-PCR) and the levels of apoptotic cells with a terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling(TUNEL) kit.


RESULTS
(1)Hemodynamic: The tendency of left ventricular end systolic pressure (PES), maximal rates of rise of ventricular pressure(dp/dtmax), maximal rates of decline of ventricular pressure (dp/dtmin) in II, III and IV groups were lower (P<0.01), time constant of left ventricular relaxation (Tc) and left ventricular end diastolic pressure (PED) were higher than those of the I group (all P<0.01). There was no difference between I and II group except PED (P<0.05). Compared with III group, PES, dp/dtmax, dp/dtmin in IV group were dramatically decline (P<0.05): Tc, PED were markedly increased (Tc P<0.05, PED P<0.01). (2)The levels of beta3-AR mRNA and beta3-AR proteins were higher in III and IV groups when compared with I and II groups. There was no difference between I and II group. IV group's levels were higher than III group's. (3)The apoptotic rates in III group and IV group were significantly higher than those in I and II group (all P<0.01). When compared with III group's apoptotic cell rate, IV group's was higher (P<0.01).


CONCLUSIONS
The levels of beta(3)-AR mRNA and proteins show an increase in failing heart compared with nonfailing heart. The effect of beta(3)-AR agonist aggravate markedly cardiac function and stimulate cardiac myocytes apoptosis in failing heart. If the levels of beta(3)-AR were too high, they might contribute to the loss of cardiac function and be the foundation of the functional degradation of HF.
Kong
Yi-hui
YH
Department of Cardiology, the First Clinical College of Harbin Medical University, Harbin 150001, Heilongjiang, China.
Li
Wei-min
WM
Tian
Ying
Y
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D022702:Receptors, Adrenergic, beta-3 / Q000032:analysis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000318:Adrenergic beta-Agonists; D012333:RNA, Messenger; D022702:Receptors, Adrenergic, beta-3