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Blockade of the Renin–Angiotensin System Attenuates Sarcolemma and Sarcoplasmic Reticulum Remodeling in Chronic Diabetes
Author(s) -
LIU XUELIANG,
SUZUKI HIDEAKI,
SETHI RAJAT,
TAPPIA PARAMJIT S.,
TAKEDA NOBUAKIRA,
DHALLA NARANJAN S.
Publication year - 2006
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1372.003
Subject(s) - sarcolemma , endoplasmic reticulum , renin–angiotensin system , medicine , diabetes mellitus , blockade , endocrinology , chemistry , cardiology , skeletal muscle , receptor , blood pressure , biochemistry
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, Ca 2+ pump, Na + ‐dependent Ca 2+ ‐uptake, Ca 2+ ‐channel density, and low‐affinity Ca 2+ ‐binding activities were depressed whereas Ca 2+ ecto‐ATPase activity was increased in the diabetic heart. Furthermore, the SR Ca 2+ ‐release and Ca 2+ ‐pump activities in the diabetic hearts were decreased without any changes in the Mg 2+ ‐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.