We have previously shown that immature tubules are resistant to anoxia compared to mature tubules. This tolerance is accompanied by an exuberant production of activated heat shock transcription factor. To further assess the role of the stress response, in vivo ischemia was produced in immature and mature rats. Immature rats (IR), age 10 days, and mature rats(MR), age 10 weeks, underwent 45 min of bilateral renal artery ischemia(BRAI); 24 hrs later, serum creatinine (Cr) was drawn and kidneys were prepared for histologic evaluation. Serum Cr (mg/dl) confirmed tolerance to ischemia (I): non-I: 0.60 ± 0.03 IR, 0.45 ± 0.05 MR, (P=NS), I: 0.66 ± 0.02 IR; 2.5 ± 0.57 MR (p<0.05). Histologic sections of the immature cortex did not show the typical morphologic changes of ischemia as were seen in the MR. To study the stress response, elaboration of HSP-72 was assessed by Western analysis under non-ischemic conditions, and after 45 min BRAI with reflow 15 min, 2 hr, 6 hr in both IR and MR. Cellular polarity was assessed by determining Na/K-ATPase in both supernatant and pellet and quantitated by densitometry. HSP-72 expression at 2 hr and 6 hr was similar in IR and MR. A major difference was noted in non-ischemic animals; HSP-72 expression in IR was 2-4 fold greater than in MR. The proportion of Na/K-ATPase in the supernatant was similar in both MR and IR under non-ischemic conditions: 4% IR, 8% MR. After 45 min BRAI, the proportion of soluble Na/K-ATPase was significantly greater in MR as compared to IR at each reflow interval: 15 min 6% IR, 29% MR; 2 hr 7% IR, 33% MR; 6 hr 15% IR, 71% MR.

In summary: 1) Tolerance in IR is maintained after 45 min BRAI. 2) HSP-72 expression in IR was 2-4 fold greater than MR in non-ischemic conditions. 3) Following 45 min BRAI, HSP-72 is similar at each reflow interval. 4) IR demonstrate less loss of cellular polarity following ischemia. This cytoprotection may be related to higher levels of HSP-72 prior to injury.