Effects of enalapril treatment on gene expression of smooth muscle myosin heavy chain isoforms in glomeruli of diabetic rats.
We have previously shown that smooth muscle contains three types of myosin heavy chains: SM1, SM2, and SMemb. The present study was designed to assess how glomerular expression of mRNA for these isoforms is regulated and whether their expression is affected by enalapril treatment in diabetic rats. Animals were divided into 4 groups: (1) untreated diabetic rats; (2) enalapril-treated diabetic rats; (3) untreated control rats, and (4) enalapril-treated control rats. Enalapril treatment was continued for 24 weeks. The glomerular mRNA levels for SM1 and SM2 showed little change in all groups throughout the experimental period. In contrast, SMemb mRNA in group 1 increased significantly with age compared to levels found in untreated controls (4.6-fold higher at 4 weeks, p < 0.01; 6.8-fold higher at 12 weeks, p < 0.01, and 10.6-fold higher at 24 weeks, p < 0.001). Enalapril reduced both creatinine clearance (p < 0.01) and urinary protein excretion (p < 0.01) in diabetic rats. Moreover, enalapril significantly attenuated the increase in the glomerular SMemb mRNA level in diabetic rats (the difference between treated and untreated rats was significant at p < 0.01 from week 4 to 24). However, enalapril had no effect on SMemb mRNA levels in controls. These data suggest that SMemb is a molecular marker for phenotypic alteration and that the beneficial effect of enalapril on proteinuria and renal function may be, at least in part, associated with reducing SMemb mRNA expression in diabetic glomeruli.
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D015152:Blotting, Northern; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004656:Enalapril / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D018995:Myosin Heavy Chains / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000806:Angiotensin-Converting Enzyme Inhibitors; D001786:Blood Glucose; D012333:RNA, Messenger; D004656:Enalapril; D018995:Myosin Heavy Chains