Different effects of angiotensin II and catecholamine on renal cell apoptosis and proliferation in rats

Background. We have recently found that chronic infusion of angiotensin II (Ang II) into rats resulted in an impairment of renal function, whereas nor epinephrine (NE) infusion did not. We investigated whether chronic infusion of Ang II and NE caused different degrees of renal cell apoptosis and prol iferation. Methods. Rats were made hypertensive via continuous infusion of either Ang II or NE for up to seven days. Renal cell apoptosis and proliferation were analyzed by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) technique and staining with antibody against prol iferating cell nuclear antigen (PCNA), respectively. In some experiments, a n inducer or inhibitor of heme oxygenase-l (HO-1) was administered to inves tigate the possible role of HO-1 in renal cell homeostasis. Results. Infusion of Ang II. but not NE, resulted in approximately a sevenf old increase in bax protein at seven days of infusion. The TUNEL assay reve aled that Ang II infusion significantly increased the number of apoptotic c ells, whereas NE infusion did not. TUNEL- and PCNA-positive cells were main ly seen in the tubulointerstitial region of Ang II-infused rats. Ang II ind uced increased positivity of TUNEL, and PCNA was blocked completely by losa rtan, but only partially by hydralazine. Induction of HO-1 reduced and inhi bition of HO increased Ang II-induced cell proliferation. Conclusions. These data suggest that Ang II plays a pivotal role in the dev elopment of renal cell proliferation and apoptosis in the setting of hypert ension. The renal HO system may modulate proliferative and pro-apoptotic ef fects of Ang II.