P-361: Captopril and L158809 treatment prevents early apoptosis in the myocardium of spontaneously hypertensive rats (SHR)

• Published in: American journal of hypertension 2001-04, Vol.14 (S1), p.151A-151A
• Main Authors: Sirous, Zohreh, Kelley, KaShonda, Klett, Christoph P. R.
• Format: Article
• Language: English
• Subjects: Apoptosis; Hypertension; Myocardium
• ISSN: 0895-7061; 1941-7225; 1879-1905
• DOI: 10.1016/S0895-7061(01)01957-4

Left ventricular (LV) fibroblasts play a crucial role in the synthesis, maintenance and degradation of the extracellular matrix in the myocardium. It is anticipated that changes in fibroblast phentoypes result in a different pattern of extracellular matrix proteins synthesized by these cells. Fibroblasts can change phenotypes effectively because of their capability to proliferate. One potential mechanism to control the phenotype of fibroblasts is apoptosis. In vitro studies have shown that an increased sensitivity to apoptotic stimuli in SHR fibroblasts exist at the age of 1 - 4 weeks. In vivo, the apoptotic response is most expressed in the left ventricle of SHRs at the age of 4 weeks within the fibroblast population. In our current study we analyzed how treatment of newborn rats with Captopril or L158809, an angiotensin II Type 1 receptor antagonist, affect the apoptotic response in the SHR. Hearts were collected at the age of 4 weeks for the preparation of cryosections. The frozen sections were subjected to various staining protocols including protocols for the detection of DNA fragmentation (FragEL) and for the immunohistochemical identification of apoptotic markers (bax, bcl2, fas). Microscopic sections were analyzed by the computer program ImagePro. In untreated SHR, DNA fragmentation was significantly increased at the age of 4 weeks when compared to corresponding sections of the WKY rat. Similar results were found for the expression of bax and fas, while the expression of bcl2 was significantly reduced. Captopril (400 mg/l) and L158809 (15 mg/l) treatment administered through the milk of the mother resulted in a significant reduction of the apoptotic events in SHR at the age of 4 weeks. In summary, an early apoptotic peak exists in SHR LV fibroblasts. Apoptotic events in the SHR may be involved to direct fibroblast phenotypes. Angiotensin systems seem to participate in directing apoptotic events in the myocardium. STUDIES WERE SUPPORTED BY AHA 9950874V AND NIH HL51971