LOOP DIURETICS REDUCE HYPOXIC DAMAGE TO PROXIMAL TUBULES OF THE ISOLATED-PERFUSED RAT-KIDNEY

The straight portion (S3) of the proximal tubule lies in close proximi ty to the thick ascending limbs (TALs) at the cortico-medullary juncti on. Since a delicate balance exists between oxygen demand and the limi ted oxygen supply in this region, we hypothesized that reduction of th ick limb metabolic activity might augment oxygen availability to S3 se gments, which depend heavily upon aerobic metabolism, and prevent hypo xic damage. The degree of functional deterioration and morphological d amage to S3 was assessed in isolated rat kidneys perfused with an eryt hrocyte-free medium. Bumetanide (10(-5) M) and furosemide (10(-4) M) r educed S3 fragmentation from 9.8 +/- 3.9% of tubules in controls to 0 and 1.4 +/- 0.9%, respectively (P < 0.0005). Tubular glucose reabsorpt ion was better preserved in kidneys exposed to loop diuretics than in control kidneys (P < 0.01), and urinary alkaline phosphatase (P < 0.05 ) and the total amount of LDH released into the perfusate and urine (P < 0.01) were lower in the treatment groups. Morphological damage to S 3 was closely correlated with medullary TAL necrosis (r = 0.66, P < 0. 001), urinary alkaline phosphatase excretion (r = 0.89, P < 0.001) and glycosuria (r = 0.83, P < 0.001). We conclude that under hypoxic cond itions TALs and S3 segments may compete with each other for a limited oxygen supply. Reduction of active transport in the mTAL might augment oxygen availability to S3 segments and improve their survival.