Effects of enalapril on endothelin-1 and growth factor gene expression in diabetic rat glomeruli.
We have previously reported that the mRNA levels of endothelin (ET-1), tumor necrosis factor-alpha), (TNF-alpha), platelet-derived growth factor (PDGF)-B chain, transforming growth factor (TGF-beta), and basic fibroblast growth factor (bFGF) all increased with age in diabetic rat glomeruli. We have now assessed the effect of the angiotensin-converting enzyme inhibitor enalapril on the expression of the ET-1, TNF-alpha, PDGF-B, TGF-beta, and bFGF genes in 24-week-old rat glomeruli after streptozotocin injection. Animals were divided into controls, enalapril-treated diabetic rats, and untreated diabetic rats. Treatment continued for 24 weeks. Enalapril reduced both creatinine clearance (p < 0.001) and urinary protein excretion (p < 0.01) in diabetic rats. Enalapril produced a nonsignificant 15 mm Hg reduction in blood pressure in diabetic rats. Enalapril also attenuated the increases in ET-1 mRNA levels observed in the glomeruli of diabetic rats (0.5-fold compared with untreated diabetic rats at 24 weeks [p < 0.01]) but had no effect on increased mRNA levels of TNF-alpha, PDGF-B, TGF-beta, and bFGF. These findings suggest that enalapril therapy may be effective in reducing ET-1 mRNA expression in the glomeruli of diabetic nephropathy.
Fukui
M
M
Department of Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Nakamura
T
T
Ebihara
I
I
Makita
Y
Y
Osada
S
S
Tomino
Y
Y
Koide
H
H
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000235:genetics*; D004656:Enalapril / Q000494:pharmacology*; D016232:Endothelins / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects*; D006133:Growth Substances / Q000235:genetics*; D007678:Kidney Glomerulus / Q000503:physiopathology*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D016232:Endothelins; D006133:Growth Substances; D012333:RNA, Messenger; D004656:Enalapril