Endothelin-1 enhances superoxide and prostaglandin E2 production of isolated diabetic glomeruli.
Endothelin-1 (ET-1) plays an important role in the pathogenic mechanism of diabetic nephropathy. However, the regulatory effects of ET-1 on superoxide and prostaglandin E2 (PGE2) in diabetic glomeruli are unclear. The aim of this study was to determine whether ET-1 exerts a differential effect on the production of superoxide and PGE2 in diabetic glomeruli. The regulatory effects of indomethacin, insulin, dexamethasone, and heparin were also investigated. Freshly isolated glomeruli were obtained from normal and streptozotocin-induced diabetic rats for 1 week (DM1W), 1 month (DM1M), and 3 months (DM3M), respectively. Our results showed that the basal superoxide production of isolated glomeruli was significantly higher in DM1M and DM3M than in the normal rats (p < 0.01). ET-1 stimulated superoxide production in normal, DM1W and DM1M glomeruli (p < 0.01) but not in DM3M rats. The basal production of PGE2 in isolated glomeruli did not differ between diabetic and normal rats. ET-1 also stimulated PGE2 production in diabetic rats (p < 0.05). Pretreatment with indomethacin further enhanced ET-1-stimulated superoxide production in all groups of diabetic rats (p < 0.05), while the ET-1-stimulated PGE2 production was attenuated by indomethacin. Insulin, dexamethasone and heparin had no additional effects on ET-1-mediated superoxide and PGE2 production. In conclusion, basal glomerular production of superoxide but not PGE2 was increased in the diabetic glomeruli. ET-1 further stimulated production of both superoxide and PGE2. Indomethacin could enhance ET-1-stimulated superoxide production while attenuating PGE2 production.
Lee
Jia-Jung
JJ
Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Hung
Chi-Chih
CC
Tsai
Jer-Chia
JC
Chen
Hung-Chun
HC
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000378:metabolism*; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism*
D019332:Endothelin-1; D013481:Superoxides; D015232:Dinoprostone