SUPPORT OF RENAL BLOOD-FLOW AFTER ISCHEMIC-REPERFUSION INJURY BY ENDOGENOUS FORMATION OF NITRIC-OXIDE AND OF CYCLOOXYGENASE VASODILATOR METABOLITES

1 Ischaemia-reperfusion injury in the kidney is associated with a loss of autoregulation, an increase in renal vascular resistance (RVR), a decrease of renal blood flow (RBF) and ultimately acute renal failure. The aim of this study was to investigate the role of the release of e ndogenous nitric oxide (NO) in the recovery of RBF after ischaemic inj ury of the renal vascular bed. 2 Anaesthetized rats (thiopentone sodiu m; 120 mg kg-1, i.p.) were submitted to acute renal ischaemia followed by 2 or 6 h of reperfusion (I/R). Reperfusion was associated with a s ignificant reduction in RBF, an increase in RVR, and an impairment of the vasodilator effect of acetylcholine (ACh). 3 N(G)-nitro-L-arginine methyl ester (L-NAME, 30 mug kg-1 min-1, i.v., n = 5) significantly p revented the recovery of RBF after I/R injury. Similarly, inhibition o f prostanoid formation with indomethacin (5 mg kg-1, i.v., n = 4) sign ificantly enhanced the rise in RVR associated with I/R injury. 4 Infus ion of L-arginine (L-Arg; 1 or 3 mg kg-1 min-1, i.v., n = 5 and 4, res pectively) or D-Arg (I mg kg-1 min-1, i.v., n = 6), starting 30 min af ter occlusion, did not improve the recovery of RBF. FurtherMore, infus ion of L-Arg (20 mg kg-1 min-1 for 15 min; n = 4) had no effect on the I/R-induced impairment of the vasodilator responses to ACh. 5 To eluc idate the relative importance of the constitutive and inducible NO syn thase isoforms for the formation of NO after I/R, calcium-dependent (c onstitutive) and calcium-independent (inducible) NO synthase activitie s were measured in kidney homogenates obtained from ischaemic or non-i schaemic kidneys. A calcium-independent NO synthase activity was not d etectable in kidney homogenates obtained from either sham-operated con trol rats or from animals subjected to I/R. Moreover, dexamethasone (3 mg kg-1, i.v., 60 min prior to I/R, n = 6), an inhibitor of the induc tion of NO synthase, had no effect on either RBF or RVR in rats subjec ted to I/R. In contrast to I/R, lipopolysaccaride (LPS, endotoxin; 5 m g kg-1, i.p., n = 3) caused a significant induction of a calcium-indep endent NO synthase activity in the kidney. 6 These results confirm the importance of the release of vasodilator cyclo-oxygenase metabolites in the compromised renal circulation and indicate that the formation o f NO derived from the constitutive, but not the inducible NO synthase, is also important for the maintenance of RBF after I/R injury of the renal vascular bed.