Effect of glycerol on endothelium-derived factors in the vasculature of the rabbit kidney.
1. In the present study, endothelium-derived relaxing factor (EDRF/nitric oxide (NO)), conversion of big endothelin (ET)-1 to endothelin-1 (ET-1) and the role of reactive oxygen species were investigated in kidneys isolated from glycerol (GLY)-pretreated rabbits. 2. Acetylcholine (ACh)-induced vasodilation that is due to the release of EDRF/NO is significantly decreased, whereas big ET-1-induced vasoconstriction was increased in kidneys isolated from GLY-pretreated rabbits. 3. Pretreatment of rabbits with the xanthine oxidase inhibitor allopurinol and the NO precursor L-arginine reversed the inhibition of ACh-induced vasodilation due to GLY and protects the kidney vasculature. 4. Big ET-1, but not ET-1, responses were found to be significantly increased in kidneys isolated from GLY-pretreated rabbits. This increase is attributed to the higher conversion rate of big ET-1 to ET-1 because the ET-converting enzyme (ECE) inhibitor phosphoramidon, at a concentration of 10(-6) mol/L, causes an inhibition in the response to big ET-1 by 52.6% in normal kidneys, whereas this inhibition with the same concentration of phosphoramidon was found to be significantly decreased in kidneys isolated from GLY-pretreated rabbits. 5. The non-selective NO synthase inhibitor N(G)-nitro-L- arginine methyl ester (L-NAME) caused a significant potentiation in the vasoconstrictor response to ET-1 in normal isolated perfused rabbit kidneys. However, L-NAME did not alter the responses to ET-1 in GLY-pretreated kidneys. 6. These results indicate that accumulation of reactive oxygen species causes an inhibition in NO bioavailability. Increased conversion of big ET-1 to ET-1 may also contribute to the mechanism of vascular damage due to GLY.
Sipahi
Emine Y
EY
Department of Pharmacology, Faculty of Medicine, Gazi University, Ankara, Turkey.
Keskil
Zuhal A
ZA
Erdinç
Meral
M
Nergis
Yusuf
Y
Türker
R Kazlm
RK
Ercan
Z Sevim
ZS
D000818:Animals; D001120:Arginine / Q000502:physiology; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000008:administration & dosage; D000072396:Endothelin-Converting Enzymes; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D005260:Female; D005990:Glycerol / Q000494:pharmacology*; D007269:Injections, Intra-Arterial; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D008666:Metalloendopeptidases; D009569:Nitric Oxide / Q000378:metabolism*; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology
D019332:Endothelin-1; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D001120:Arginine; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes; D005990:Glycerol