Protection from renal ischemia reperfusion injury by an endothelin-A receptor antagonist BQ-123 in relation to nitric oxide production.
The aim of this study was to investigate whether the protective effect of endothelin-A (ET(A)) receptor antagonist BQ-123 against renal ischemia reperfusion (I/R) injury is related to nitric oxide (NO) production. Sprague-Dawley rats were divided into six groups: control, I/R, N sup omega nitro-L-arginine methyl ester (L-NAME), BQ, BQ+L-NAME, BQ+L-NAME+L-Arg groups. After urethane anesthesia, 30min renal ischemia and 2h reperfusion were performed in all groups except control group. Mean arterial pressures (MAP) during reperfusion in all L-NAME-treated groups were higher than during pre-ischemia and ischemia, however, MAP at 60th and 120th minute of reperfusion in control and BQ groups were lower than during ischemia. MAP of L-NAME-treated groups were significantly higher than the other groups during reperfusion period. The I/R caused lipid peroxidation and protein oxidation, however, BQ-123 treatment prevented oxidant injury. The inhibition of NO production prevented effect of BQ-123 treatment. Also, BQ-123 treatment caused an increase in superoxide dismutase and catalase activities. Both BQ-123 and L-NAME treatments prevented high xanthine oxidase activity. BQ-123 prevented risen myeloperoxidase activity and L-NAME reversed this effect of BQ-123 just like the addition of L-arginine to the treatment altered the effect of L-NAME. The plasma BUN was affected as increasing manner from L-NAME treatments; on the other hand, plasma Cr and Na concentrations were affected as decreasing manner from BQ-123 treatments. ET(A) receptor antagonist BQ-123 may be revealed a protective agent against renal I/R injury with a possible secondary pathway via its antioxidant effects. We suggest that BQ-123 may mediate the protective effect via a NO-dependent mechanism.
Erdogan
Hasan
H
Gaziosmanpasa University, Faculty of Medicine, Department of Physiology, TR-60100 Tokat, Turkey. haserdogan@yahoo.com <haserdogan@yahoo.com>
Fadillioglu
Ersin
E
Emre
Memet Hanifi
MH
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001806:Blood Urea Nitrogen; D002374:Catalase / Q000378:metabolism; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009929:Organ Size / Q000187:drug effects; D010456:Peptides, Cyclic / Q000494:pharmacology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000502:physiology*; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012964:Sodium / Q000097:blood; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D010456:Peptides, Cyclic; D017392:Thiobarbituric Acid Reactive Substances; D009569:Nitric Oxide; D012964:Sodium; D002374:Catalase; D009195:Peroxidase; D005979:Glutathione Peroxidase; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D019331:NG-Nitroarginine Methyl Ester