RENAL MICROCIRCULATION AND TISSUE-DAMAGE DURING ACUTE URETERAL OBSTRUCTION IN THE RAT - EFFECT OF SALINE INFUSION, INDOMETHACIN AND RADIOCONTRAST

Radiocontrast agents and nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used for the diagnosis and treatment of renal colic. We studied their impact during unilateral acute urinary outflow obstructi on upon renal microcirculation and parenchymal integrity. Laser-Dopple r and ultrasonic regional flow measurements demonstrated selective dec line of outer medullary blood flow by 23 +/- 2% during an acute increa se of intra-pelvic pressure to 50 to 55 cm H2O (N = 28, X +/- SEM, P < 0.01). In rats preconditioned with indomethacin, this manipulation re duced medullary blood flow by 50 +/- 4% (N = 16, P < 0.01 vs. obstruct ion alone), with cortical and total renal blood flow declining by 18 /- 4% and 16 +/- 2%, respectively (P < 0.01). Unilateral obstruction a lone for 24 hours in intact rats resulted in injury (hemorrhage and ne crosis) to the papilla and fornix (formed laterally by inner stripe an d medially by the inner medulla). These changes were detected as early as 30 minutes after ureteral ligature by staining for fragmented nucl ear DNA (TUNEL). Mild damage of thick ascending limbs (mTALs) was asso ciated with substantial medial fornix injury. Indomethacin markedly in creased mTAL injury in obstructed kidneys, but attenuated inner medull ary damage, both in the medial border of the urinary space and at the papilla. This latter protective effect, probably mediated by the decre ase in intrapelvic pressure, was blunted by concomitant intravenous fl uid load. Contrast media (iothalamate) and L-NAME (N-omega nitro-L-arg inine methyl ester) both augmented inner stripe and inner medullary da mage in hydronephrotic kidneys. In rats concomitantly subjected to rad iocontrast, indomethacin and L-NAME (an acute renal failure protocol, J Clin Invest 94:1069, 1994), unilateral obstruction augmented inner s tripe hypoxic damage (65 +/- 6% vs. 24 +/- 11% of mTALs in contralater al kidneys, N = 7, P < 0.01). Injury was maximal at the fornix (93 +/- 6% vs. 39 +/- 14% of mTALs in the mid-inner stripe, P < 0.01) and ext ended to the outer stripe and medullary rays. Thus, in the rat acute u reteral obstruction alters medullary blood flow and within 24 hours pr oduces medullary damage in both forniceal and inner medullary location s, that is exacerbated by concomitant measures which limit medullary o xygenation. Contrast stud ies, forced hydration and NSAIDs for renal c olic are potentially harmful and their use should be re-evaluated.