p53-mediated upregulation of BAX gene transcription is not involved in Bax-alpha protein overexpression in the left ventricle of spontaneously hypertensive rats

An association of increased apoptosis with overexpression of the proapoptot ic protein Bax-alpha has been reported in the left ventricle of adult spont aneously hypertensive rats (SHR). Both alterations were corrected in SHR th at received long-term treatment with the AT, antagonist losartan. To gain i nsight into the regulation of cardiac Bax-alpha protein in genetic hyperten sion, we investigated the expression of the protein p53 (a BAX gene transcr iption factor) and BAX mRNA in the left ventricle of 30-week-old Wistar-Kyo to rats (WKY), SHR, and SHR treated with losartan (20 mg.kg(-1).d(-1)) duri ng 14 weeks before death. The expression of p53 and Bax proteins was assess ed by Western blot analysis. The expression of BAX mRNA was assessed by Nor thern blot analysis. The density of apoptotic cells was assessed by direct immunoperoxidase detection of biotin-labeled deoxyuridine nucleotides. Comp ared with WKY, untreated SHR exhibited increased apoptosis (P<0.05), increa sed Bax-alpha protein (P<0.05), and similar levels of p53 protein and BAX m RNA, Losartan given long term. was associated with the normalization of apo ptosis and Bax-alpha protein expression. The expression of BAX mRNA was dec reased (P<0.05) in treated SHR compared with untreated SHR. No changes in t he expression of p53 protein were observed in losartan-treated SHR. These r esults suggest that overexpression of the Bax-alpha protein seen in the lef t ventricle of adult SHR with increased apoptosis is not related to a p53-m ediated upregulation of BAX gene transcription. Our data also suggest that normalization of Bax-alpha protein observed in SHR after long-term blockade of angiotensin II type 1 receptors may be due to the inhibition of BAX gen e transcription.