Renin-angiotensin blockade attenuates cardiac myofibrillar remodelling in chronic diabetes.
Previous studies have shown that the renin-angiotensin system (RAS) is activated in diabetes and this may contribute to the subcellular remodelling and heart dysfunction in this disease. Therefore, we examined the effects of RAS blockade by enalapril, an angiotensin-converting enzyme inhibitor, and losartan, an angiotensin receptor AT1 antagonist, on cardiac function, myofibrillar and myosin ATPase activity as well as myosin heavy chain (MHC) isozyme expression in diabetic hearts. Diabetes was induced in rats by a single injection of streptozotocin (65 mg/kg; i.v.) and these animals were treated with and without enalapril (10 mg/kg/day; oral) or losartan (20 mg/kg/day; oral) for 8 weeks. Enalapril or losartan prevented the depressions in left ventricular rate of pressure development, rate of pressure decay and ventricular weight seen in diabetic animals. Both drugs also attenuated the decrease in myofibrillar Ca2+-ATPase, Mg2+-ATPase and myosin ATPase activity seen in diabetic rats. The diabetes-induced increase in beta-MHC content and gene expression as well as the decrease in alpha-MHC content and mRNA levels were also prevented by enalapril and losartan. These results suggest the occurrence of myofibrillar remodelling in diabetic cardiomyopathy and provide evidence that the beneficial effects of RAS blockade in diabetes may be associated with attenuation of myofibrillar remodelling in the heart.
Machackova
Jarmila
J
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre; Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
Liu
Xueliang
X
Lukas
Anton
A
Dhalla
Naranjan S
NS
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002908:Chronic Disease; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D004656:Enalapril / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006352:Heart Ventricles / Q000737:chemistry / Q000201:enzymology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009210:Myofibrils / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D018995:Myosin Heavy Chains / Q000378:metabolism; D009218:Myosins / Q000032:analysis / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects*
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D004656:Enalapril; D018995:Myosin Heavy Chains; D009218:Myosins; D019808:Losartan