Abstract-Various renal insults result in induction of heat shock protein (HSP) expression within the kidney. Some of the HSPs induced in that manner are postulated to have renoprotective effects via either chaperoning actions or antioxidative properties. We have previously reported that long-term angiotensin (Ang) II administration induces the expression of renal HSP32, also known as heme oxygenase-1 (HO-1). Here, we investigated the regulation of expression and localization of other HSPs, including HSP70, HSP25, and ␣B-crystallin, in the kidney of rats undergoing long-term administration of Ang II (0.7 mg · kg. Immunoblot analysis demonstrated that Ang II increased renal expression of HSP70 and HSP25, as well as HO-1, but that expression of ␣B-crystallin was unaffected by this treatment. The Ang II-induced increase in renal HSP70 and HSP25 was dependent on the angiotensin type 1 receptor activation but not on hypertension per se. Immunohistochemistry revealed that HSP70 and HSP25 were expressed in the medullar regions and in the renal arterial wall in the kidney of control rats. After Ang II infusion, signals for HSP70, HSP25, and HO-1 proteins increased in intensity in the endothelium and medial smooth muscle of the renal artery. In addition, all of these HSPs were induced in proximal renal tubular epithelial cells from the same segments, suggesting that similar mechanisms are responsible for upregulating these HSPs. Our data show that Ang II infusion induces renal HSP70 and HSP25, as well as HO-1, and that Ang II can induce expression of these HSPs in renal cells in a pressor-independent manner. 4 Previous studies have demonstrated that several HSPs, including HSP32 (also known as heme oxygenase-1, HO-1), 5 HSP25, HSP60, HSP70/HSP72, HSP73, 6 and ␣B-crystallin, 7 are present in the kidney.HO-1/HSP32, an inducible form of HO, catalyzes the rate-limiting step in the degradation of heme. Induction of renal HO-1 has been shown to ameliorate renal injury induced by rhabdomyolysis. 8 Gene ablation of HO-1 exacerbated cisplatin-induced renal tubular injury. 9 Thus, the intrarenal HO system is thought to play a role in protecting renal function against various renal insults. The inducible form of HSP70 is also shown to be regulated in the kidney in response to stimuli such as ischemia 7 and hyperthermia. 10 Overexpression of transfected HSP70 in the renal cells was found to have a protective action against cisplatin toxicity, oxidative injury, 11 and hyperthermia. 12 HSP25 and ␣B-crystallin are both members of the low-molecular-weight HSP family. They can be phosphorylatable at various amino acid positions, although their phosphorylation may not be essential for their chaperoning properties. 13 Renal expression of HSP25 and ␣B-crystallin is known to be regulated, 7,14 but their precise biological role in the kidney remains unclear.We have recently shown that HO-1 is induced in tubular epithelial cells in response to administration of angiotensin (Ang) II and that the increased levels of HO-1 may play a role in ameli...