Modification of myosin protein and gene expression in failing hearts due to myocardial infarction by enalapril or losartan.
The effects of enalapril, an angiotensin converting enzyme (ACE) inhibitor, and losartan, an angiotensin II receptor type I antagonist, were investigated on alterations in myofibrillar ATPase activity as well as myosin heavy chain (MHC) content and gene expression in failing hearts following myocardial infarction (MI). Three weeks after ligation of the left coronary artery, rats were treated with or without enalapril (10 mg/kg/day), and/or losartan (20 mg/kg/day) for 5 weeks. The infarcted animals exhibited an increase in left ventricle (LV) end diastolic pressure and depressed rates of LV pressure development as well as pressure decay. LV myofibrillar Ca2+ -stimulated ATPase activity was decreased in the infarcted hearts compared with controls, MHC alpha-isoform content was significantly decreased whereas that of MHC beta-isoform was markedly increased. The level of MHC alpha-isoform mRNA was decreased whereas that of MHC beta-isoform was increased in the viable infarcted LV. Treatment of animal with enalapril, losartan, or combination of enalapril and losartan partially prevented the MI induced changes in LV function, myofibrillar Ca2+ -stimulated ATPase activity, MHC protein expression and MHC gene expression. The results suggest that the beneficial effects of the renin-angiotensin system blockade in heart failure are associated with partial prevention of myofibrillar remodeling.
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Canada.
Jingwei
J
Wang
Xiaobing
X
Guo
Naranjan S
NS
Dhalla
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D015152:Blotting, Northern; D002118:Calcium / Q000378:metabolism; D003971:Diastole; D004656:Enalapril / Q000494:pharmacology*; D005786:Gene Expression Regulation; D015151:Immunoblotting; D019808:Losartan / Q000494:pharmacology*; D008274:Magnesium / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000378:metabolism; D009218:Myosins / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D020033:Protein Isoforms; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D016277:Ventricular Function, Left
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D020033:Protein Isoforms; D012333:RNA, Messenger; D012313:RNA; D004656:Enalapril; D000251:Adenosine Triphosphatases; D018995:Myosin Heavy Chains; D009218:Myosins; D008274:Magnesium; D019808:Losartan; D002118:Calcium