[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.
Department of Cardiology, the First Clinical College of Harbin Medical University, Harbin 150001, Heilongjiang, China.
Yi-hui
YH
Kong
Wei-min
WM
Li
Ying
Y
Tian
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