Blockade of the renin-angiotensin system attenuates sarcolemma and sarcoplasmic reticulum remodeling in chronic diabetes.
Although the defects in the sarcolemma (SL) and sarcoplasmic reticulum (SR) membranes are known to be associated with cardiac dysfunction in chronic diabetes, very little information regarding the mechanisms of these membrane abnormalities is available in the literature. For this reason, rats were treated daily for 8 weeks with and without enalapril, an angiotensin-converting enzyme inhibitor, or losartan, an angiotensin receptor antagonist, 3 days after inducing diabetes with an injection of streptozocin. Treatment of diabetic animals with both enalapril and losartan attenuated alterations in cardiac function and the left ventricular redox potential without any changes in the increased plasma glucose or reduced plasma insulin levels. The SL Na+-K+ ATPase, Ca2+ pump, Na+-dependent Ca2+-uptake, Ca2+-channel density, and low-affinity Ca2+-binding activities were depressed whereas Ca2+ ecto-ATPase activity was increased in the diabetic heart. Furthermore, the SR Ca2+-release and Ca2+-pump activities in the diabetic hearts were decreased without any changes in the Mg2+-ATPase activity. These alterations in SL and SR membranes in diabetic animals were partly prevented by treatments with enalapril and losartan. The results suggest that the activation of the renin-angiotensin system plays an important role in diabetes-induced changes in SL and SR membranes as well as cardiac function.
Liu
Xueliang
X
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, 351 Tache Avenue, Winnipeg, Manitoba, Canada R2H 2A6.
Suzuki
Hideaki
H
Sethi
Rajat
R
Tappia
Paramjit S
PS
Takeda
Nobuakira
N
Dhalla
Naranjan S
NS
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000188:drug therapy; D004656:Enalapril / Q000627:therapeutic use; D019808:Losartan / Q000627:therapeutic use; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D012508:Sarcolemma / Q000502:physiology*; D012519:Sarcoplasmic Reticulum / Q000502:physiology*; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology / Q000517:prevention & control; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D008315:Malondialdehyde; D004656:Enalapril; D019808:Losartan