Alteration of endothelin system and calcium handling protein in left ventricles following drug treatment in dilated cardiomyopathy rats.
OBJECTIVE
To investigate the changes of cardiac calcium handling proteins and endothelin system in dilated cardiomyopathy (DCM) rats and the effects of perindopril and bisoprolol on the remodeling ventricles.


METHODS
DCM rats were employed using a 2-kidney, 1-clip hypertensive and diabetic model. Some of the DCM rats were treated with perindopril and bisoprolol for 3 months, respectively. The ratio of left ventricular weight to body weight (LVW/BW), mRNA expressions of calcium handling proteins and endothelin receptors were determined. The alterations of maximum binding capacity (Bmax) and equilibrium dissociation constant (KD) values of cardiac endothelin receptors (ETR) and its subtypes were detected.


RESULTS
Compared with those of normal control, blood pressure, and LVW/BW in the DCM rats were elevated. Sarcoplasmic reticulum calcium pump (SERCA) mRNA expression and SERCA activity decreased in the left ventricle. The ETR Bmax decreased, especially the endothelin receptor A. Endothelin converting enzyme activity and expression were elevated, and mRNA expressions of beta1-adrenoreceptor and inositol-3-phosphate receptor in some hearts increased as well. The administration of perindopril and bisoprolol could reverse myocardial hypertrophy and restore the imbalance of calcium handling proteins and endothelin system.


CONCLUSIONS
The disorder of calcium handling proteins and endothelin system existed in the hearts of DCM rats. Treatment of perindopril and bisoprolol could reverse myocardial hypertrophy and changes in DCM rats.
Zhang
Ji-Nan
JN
Research Institute of Cardiovascular Disease, First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China. jinanzh@sina.com
Geng
Qian
Q
Chen
Xiang-Jian
XJ
Fang
Wu-Wang
WW
Wu
Xiao-Hui
XH
Yang
Di
D
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D017298:Bisoprolol / Q000494:pharmacology; D015220:Calcium Channels / Q000096:biosynthesis / Q000235:genetics; D000252:Calcium-Transporting ATPases / Q000096:biosynthesis* / Q000235:genetics; D002311:Cardiomyopathy, Dilated / Q000378:metabolism*; D006352:Heart Ventricles; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D020913:Perindopril / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018342:Receptors, Adrenergic, beta-1 / Q000096:biosynthesis / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis / Q000235:genetics; D017466:Receptors, Endothelin / Q000096:biosynthesis* / Q000235:genetics; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D012333:RNA, Messenger; D018342:Receptors, Adrenergic, beta-1; D018160:Receptors, Cytoplasmic and Nuclear; D017466:Receptors, Endothelin; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D017298:Bisoprolol; D020913:Perindopril