Renal functional responses to ischaemia-reperfusion injury in normotensive and hypertensive rats following non-selective and selective cyclo-oxygenase inhibition with nitric oxide donation.
1. Acute renal failure develops as a result of periods of renal ischaemia during cardiovascular surgery or hypovolaemic shock. The present study investigated the importance of endogenous prostaglandin production and nitric oxide (NO) in the renal haemodynamic and excretory responses to ischaemia-reperfusion both normally and in the hypertensive state by chronic administration of cyclo-oxygenase (COX) inhibitors. 2. Male Wistar and stroke-prone spontaneously hypertensive rats (SHRSP) were subjected to 30 min renal ischaemia and 2 h reperfusion following 7 day treatment with vehicle, aspirin, NO-aspirin or celecoxib. 3. Renal blood flow was higher in the SHRSP treatment groups. Renal ischaemia increased blood pressure in all Wistar groups except that given aspirin, had no effect in the SHRSP and did not change renal blood flow in any group. Glomerular filtration rate was reduced throughout the reperfusion period in both rat strains. The postischaemic diuresis in the Wistar was enhanced by COX-2 inhibition, but not by aspirin or NO-aspirin. Urine flow increased in SHRSP during the postischaemic period, which was blunted by aspirin and NO-aspirin, but not by celecoxib. There was a postischaemic increase in fractional sodium excretion, the magnitude of which was unaltered by any drug in the Wistar rats, but was blunted by aspirin, NO-aspirin and celecoxib in SHRSP. 4. These results suggest that products of COX activity contribute to the renal responses to ischaemia-reperfusion injury, but in different ways, in SHRSP, which may reflect variations in renal prostaglandin and NO production in the hypertensive state.
Department of Physiology, Aras Windle, University College Cork, Cork, Republic of Ireland.
Sarah
S
Knight
Edward J
EJ
Johns
D000818:Animals; D001241:Aspirin / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D000068579:Celecoxib; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004231:Diuresis / Q000187:drug effects; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009566:Nitrates / Q000494:pharmacology* / Q000627:therapeutic use; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology* / Q000627:therapeutic use; D011453:Prostaglandins / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D012964:Sodium / Q000652:urine; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D008565:Membrane Proteins; C488176:N-acetyl-S-(alpha-methyl-4-(2-methylpropyl)benzeneacetyl)cysteine 4-(nitrooxy)butyl ester; D009566:Nitrates; D020030:Nitric Oxide Donors; D011453:Prostaglandins; D011720:Pyrazoles; D013449:Sulfonamides; D009569:Nitric Oxide; D012964:Sodium; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496513:Ptgs1 protein, rat; C489691:Ptgs2 protein, rat; D000068579:Celecoxib; D001241:Aspirin