Role of Nitric Oxide in Renal Medullary Oxygenation Studies in Isolated and Intact Rat Kidneys

We investigated the role of the endothelial-derived relaxing factor nitric oxide (NO) in the homeostasis of 02 supply to the renal medulla, a region normally operating on the verge of hyp-oxia. Sensitive Clark-type 02 microelectrodes were inserted into renal cortex and medulla of anesthetized rats. The inhibi-tor of NO formation,-NM-monomethylarginine (LNMMA), while increasing blood pressure and reducing renal blood flow, decreased medullary P02 from 23±3 mmHg to 12±3 (P < 0.001), with no change in the cortex. These responses were promptly reversed by L-arginine, which bypasses theLNMNMA blockade. In isolated rat kidneys, LNMMA reduced perfusion flow without altering glomerular filtration rate, and augmented deep medullary hypoxic injury to thick ascending limbs from 68 to 90 % ofthe tubules (P < 0.02). These changes were prevented by L-arginine. Nitroprusside had a protective effect upon thick limb injury. Finally, in a previously reported model ofradiocon-trast nephropathy (1988. J. Clin. Invest. 82:401), LNMMA increased the severity of renal failure (final plasma creatinine from 2.3±2 mg%0 to 3.4±3, P < 0.005) and the proportion of damaged thick limbs (from 24±6 % to 53±9, P < 0.01). Nitrovasodilatation may participate in the balance of renal medullary oxygenation and play an important role in the pre-vention of medullary hypoxic injury. (J. Clin. Invest. 1991. 88:390-395.) Key words: renal medulla * thick ascending limb. oxygen microelectrode * contrast medium * indomethaci