Angiotensin II augments medullary hypoxia and predisposes to acute renal failure

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Abstract
The effects of angiotensin II (AII) upon medullary hypoxic injury and kidney function were investigated in vitro and in vivo. Synthetic AII added to perfusate of isolated rat kidneys reduced perfusion flow from 48 ± 2 ml min−1 (±SE) to 19 ± 1 (P < 0·001) without altering glomerular filtration rate (GFR), raising filtration fraction from 1% to 3% (P < 0·001). AII-extended hypoxic injury to medullary thick ascending limbs (mTAL) from 66 ± 4% of tubules to 79 ± 3 (P < 0·05) in correlation with filtration fraction (r = 0·8, P < 0·001). Addition of indomethacin (10−4 mol 1−1) further extended medullary hypoxic damage to 89 ± 2% of mTAL (P < 0·001). Uninephrectomized rats kept in metabolic cages were given AII by continuous infusion (0·1–0·8 μg min−1) and indomethacin (10 mg kg−1 day−1) for 24 h. Creatinine clearance declined from 1·3 ± 0·1 ml min−1 to 0·6 ± 0·06 (P < 0·001). Morphological examination revealed either selective necrosis of mTAL (in 12 ± 4% of tubules) or luminal collapse (in 63 ± 8%). Both necrosis and collapse correlated inversely with creatinine clearance and with each other (r = −0·5, P < 0·001), the latter correlation suggesting protection from hypoxic injury by cessation of solute delivery. By increasing filtration fraction and decreasing blood flow, AII decreases renal oxygen supply while maintaining oxygen consumption for solute reasborption. AII may predispose to acute renal failure by augmenting medullary hypoxia.