High-level apoptosis is persistent in myocardiocytes of sinoaortic-denervated rats.
BACKGROUND
Arterial baroreflex plays an important part in the regulation of cardiovascular activity. Sinoaortic denervation (SAD) produces organ damage in rats. A previous study suggested that apoptosis in myocardium is involved in the organ damage induced by SAD.


OBJECTIVE
To study the time course of cardiomyocyte apoptosis in SAD rats by evaluating apoptotic cells and expression of apoptosis-related genes in the left ventricles of SAD rats, 4, 8, 16 and 32 weeks after SAD operation.


METHODS
Male Sprague-Dawley rats underwent SAD or sham operation at the age of 10 weeks. Four, 8, 16 or 32 weeks after operation, blood samples and heart tissues were taken for the following studies: determination of angiotensin II in plasma and heart, pathological evaluations, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labelling and immunohistochemistry. Some observations were also made in rats 1 and 2 weeks after denervation.


RESULTS
Loss of body weight gain, cardiac hypertrophy, an increase in left ventricular collagen volume and an increase in cardiac angiotensin II content were observed in SAD rats from 2 to 32 weeks after SAD operation. The apoptotic myocardiocytes were increased in SAD rats compared with sham-operated rats. The expression of Bcl-2 protein, an inhibiting factor of apoptosis, was markedly decreased in the myocardiocytes of SAD rats. In contrast, the expression of Bax, Fas and Fas-L proteins, promoting factors of apoptosis, was significantly increased in the myocardiocytes of SAD rats. All these modifications were persistent from 4 to 32 weeks after SAD operation.


CONCLUSIONS
These findings demonstrate that a high level of apoptosis is persistent in myocardiocytes in SAD rats. We propose that apoptosis may be one of the mechanisms underlying the cardiac damage induced by SAD.
Tao
Xia
X
Department of Pharmacology, Second Military Medical University, Shanghai, China.
Zhang
Shu-Hui
SH
Shen
Fu-Ming
FM
Su
Ding-Feng
DF
D000804:Angiotensin II / Q000097:blood; D000818:Animals; D017209:Apoptosis; D017704:Baroreflex / Q000502:physiology*; D001835:Body Weight; D006332:Cardiomegaly / Q000378:metabolism / Q000473:pathology*; D003714:Denervation; D053222:Fas Ligand Protein; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051028:bcl-2-Associated X Protein; D019014:fas Receptor / Q000378:metabolism
C494828:Bax protein, rat; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D000804:Angiotensin II