Although acute renal ischaemia alters the production of various paracrines, there has been little investigation examining the role of intrarenal vasoactive substances. In the present study, we investigated the role of intrarenal nitric oxide and prostaglandins in modulating the acute renal hypoperfusion-induced alterations in renal function. After a 90% clipping of the left renal artery for 60 min, the clip was released, and the renal haemodynamics and sodium excretion were evaluated in both clipped and non-clipped kidneys of anaesthetized dogs. Furthermore, the changes in renal contents of nitrate/nitrite (NOx) and prostaglandin E2 (PGE2) were assessed by using the renal microdialysis technique. The release of the clipping elicited a gradual recovery of renal plasma flow and glomerular filtration rate, and a sustained increase in fractional sodium excretion (FENa) in the clipped kidney. Renal interstitial NOx was reduced in both the cortex (from 8.2±1.1 to 2.5±0.3 μmol/L, P<0.01) and medulla (from 10.1 ± 0.9 to 3.1 ± 0.2 μmol/L, P<0.01), but the levels gradually elevated after declamping. The treatment with nitro-L-arginine methylester only modestly impaired the recovery of renal plasma flow (RPF; at hour 4) and glomerular filtration rate (GFR; at hours 3 and 4 after declamping), without affecting FENa. Conversely, the renal PGE2 levels increased prominently upon the onset of ischaemia (medulla, from 149±19 to 378±39 pg/mL, P<0.01; cortex, from 107±13 to 302±34 pg/mL, P<0.01). Furthermore, the pretreatment with a non-specific cyclo-oxygenase (COX) inhibitor, sulpyrine, and a COX-2-specific inhibitor, NS398, prominently inhibited the increases in FENa induced by the acute renal arterial clipping in a similar manner. In conclusion, in acute renal hypoperfusion, nitric oxide (NO) plays a permissive role in the recovery of the renal haemodynamics. In contrast, sustained increases in renal PGE2 in both clipped and non-clipped kidneys indicate that the COX-2-mediated PGE2 contributes importantly to the failure of the sodium reabsorption in response to acute renal hypoperfusion.
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