Effects of carvedilol on M2 receptors and cholinesterase-positive nerves in adriamycin-induced rat failing heart.
Heart failure is correlated with attenuation of parasympathetic nervous function and enhanced sympathetic activity. Carvedilol, a third-generation beta-blocker, may improve the prognosis of heart failure better than selective beta(1)-blockers. Not all of its effects, however, can be explained by direct actions on the sympathetic nervous system. This study was therefore performed to investigate the possible alterations of muscarinic cholinergic (M)(2) receptors and cholinesterase-positive nerves in different regions of the adriamycin-induced failing rat heart, and the potential effects of carvedilol on these M(2) receptors and cholinesterase-positive nerves. Karnovsky-Roots histochemical staining combined with point counting methods, and immunochemical streptavidin-biotin complex staining and image analysis were used to test the distribution of cholinesterase-positive nerves and the expression of M(2) receptors, respectively. Our results show that the cholinesterase-positive nerve system was downregulated in the adriamycin-induced failing heart group, while the density of M(2) receptors was increased in the carvedilol 3- and 10-mg/kg body weight groups, especially in the endocardial tissues of the left-ventricular free wall. It is concluded that upregulation of M(2) receptors may be one of the potential mechanisms by which carvedilol exert its action on heart failure.
Xu
Xiao-Li
XL
Division of Cardiovascular Physiology and Pharmacology, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
Zang
Wei-Jin
WJ
Lu
Jun
J
Kang
Xin-Qin
XQ
Li
Ming
M
Yu
Xiao-Jiang
XJ
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology* / Q000627:therapeutic use; D000077261:Carvedilol; D002802:Cholinesterases / Q000032:analysis*; D015536:Down-Regulation / Q000187:drug effects; D004317:Doxorubicin / Q000633:toxicity; D004699:Endocardium / Q000187:drug effects / Q000294:innervation; D006325:Heart Atria / Q000737:chemistry / Q000294:innervation / Q000473:pathology; D006329:Heart Conduction System / Q000187:drug effects* / Q000648:ultrastructure; D006333:Heart Failure / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D006352:Heart Ventricles / Q000737:chemistry / Q000294:innervation / Q000473:pathology; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects* / Q000201:enzymology; D009419:Nerve Tissue Proteins / Q000032:analysis*; D010275:Parasympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D011412:Propanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D043585:Receptor, Muscarinic M2 / Q000096:biosynthesis / Q000187:drug effects*; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy / Q000503:physiopathology
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D009419:Nerve Tissue Proteins; D011412:Propanolamines; D043585:Receptor, Muscarinic M2; D000077261:Carvedilol; D004317:Doxorubicin; D002802:Cholinesterases