Renal-specific Regulation of Apoptosis and It's Modulators by Angiotensin II

Cheon, Hae Won; Yoo, Kee Hwan

Abstract

Angiotensin II plays an important role in the regulation of systemic and renal hemodynamics, and functions as a growth factor in various tissues. To determine whether ANG II are related to renal-specific stimulation of apoptosis, 36 adult male Sprague-Dawley rats were infused with ANG II at 50 ng/min(low ANG group), 100 ng/min(high ANG group), or vehicle(control group) for 1 week using osmotic minipump(Model 1007D, Alza Co, USA) inserted into the interscapular area of the back. Blood pressure and serum aldosterone level were measured. To detect apoptosis of the kidney, TUNEL(Terminal deoxynucleotidyl Transferase dUTP Nick End Labelling) technique was introduced. Cellular proliferation was detected with PCNA immune histochemical staining. To know the expression of Bcl-2 protein and mRNA, immune histochemical staining, Western blot assay and RT-PCR were done. Results were as follows: 1) There were no differences in body weight or organ weight/body weight among 3 groups. 2) Mean blood pressure between control and low ANG group were not changed throughtout the study. But mean blood pressure was increased at th day 3 and 7 in high ANG group(P<0.05). Serum aldosterone level increased at the day 7 in high ANG group only(P<0.05). 3) PCNA positive cells were increased significantly in the the low ANG groups compared with the control group(P<0.05) and they were decreased significantly in the .high ANG group compared with the the low ANG group(P<0.05). However, they were not different between control and high ANG groups. 4) Apoptosis of renal medulla was increased significantly in the low and high ANG groups compared with the control group(P<0.05). 5) Expression of bcl-2 protein was decreased significantly in the low and high ANG groups compared with the control group(P<0.05). In this study, ANG II infusion induced renal apoptosis and changed expression of PCNA but decreased expression of bcl-2 in the kidney of the Sprague-Dawley rat. In conclusion, histologic changes of the kidney may be controlled by ANG II regardless of systemic hypertension.