The beta-adrenergic blocker carvedilol restores L-type calcium current in a myocardial infarction model of rabbit.
BACKGROUND
Carvedilol, an antagonist of alpha1- and beta-adrenergic receptors, has shown efficacy in reducing all-cause death and arrhythmia death for ischemic heart disease and congestive heart failure in several large-scale trials. It has been found to prevent ventricular remodeling, and recently was reported to reverse down-regulation of Na+ channel in a chronic heart failure model. This study was conducted to investigate whether carvedilol could reverse the ion remodeling in a myocardial infarction model of rabbit.


METHODS
After the procedure of coronary ligation, animals were randomized to placebo or carvedilol treatment (5 mg/kg). Action potentials, L-type calcium current (Ica L) and the effect of isoproterenol stimulation on Ica L were measured using whole-cell patch method. Evaluation of the expression of calcium channel subunits was carried out by RT-PCR and Western blot.


RESULTS
The results indicate that mean peak Ica L densities (pA/pF) at +10 mV was reduced in postinfarction myocytes (5.33 +/- 0.45, n = 25) compared to sham myocytes (6.52 +/- 0.21, n = 20). Treatment of myocardial infarction rabbits with carvedilol could restore it partially (5.91 +/- 0.39, n = 20, P < 0.05). However, steady-state activation parameters were similar in three groups. With stimulation by isoproterenol (1 micromol/L) Ica L increased in all three groups, but the increase was smaller in postinfarction myocytes. mRNA levels of calcium channel subunit CaA1 gene was decreased but CaB2a, CaB2b and CaB3 mRNA levels did not change after MI. Corresponding change in CaA1 protein was also observed.


CONCLUSIONS
The results demonstrate that carvedilol restores Ica L density and reverse the downregulation of CaA1 postinfarction.
Li
Xia
X
Department of Cardiology, People's Hospital of Wuhan University, Wuhan 430060, China. summermm@vip.sina.com
Huang
Cong-Xin
CX
Jiang
Hong
H
Cao
Feng
F
Wang
Teng
T
D000200:Action Potentials / Q000187:drug effects; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D020746:Calcium Channels, L-Type / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism* / Q000503:physiopathology; D011412:Propanolamines / Q000494:pharmacology*; D011817:Rabbits; D011897:Random Allocation; D020257:Ventricular Remodeling / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D020746:Calcium Channels, L-Type; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol