Cellular and molecular remodeling in a heart failure model treated with the beta-blocker carteolol.
Broad-breasted white turkey poults fed furazolidone developed dilated cardiomyopathy (DCM) characterized by ventricular dilatation, decreased ejection fraction, beta1-receptor density, sarcoplasmic reticulum (SR) Ca2+-ATPase, myofibrillar ATPase activity, and reduced metabolism markers. We investigated the effects of carteolol, a beta-adrenergic blocking agent, by administrating two different dosages (0.01 and 10.0 mg/kg) twice a day for 4 wk to control and DCM turkey poults. At completion of the study there was 59% mortality in the nontreated DCM group, 55% mortality in the group treated with the low dose of carteolol, and 22% mortality in the group treated with the high dose of carteolol. Both treated groups showed a significant decrease in left ventricle size and significant restoration of ejection fraction and left ventricular peak systolic pressure. Carteolol treatment increased beta-adrenergic receptor density, and the high carteolol dose restored SR Ca2+-ATPase and myofibrillar ATPase activities, along with creatine kinase, lactate dehydrogenase, aspartate transaminase, and ATP synthase activities, to normal. These results show that beta-blockade with carteolol improves survival, reverses contractile abnormalities, and induces cellular remodeling in this model of heart failure.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D002354:Carteolol / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D005664:Furazolidone / Q000494:pharmacology; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D006339:Heart Rate / Q000187:drug effects; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D018485:Muscle Fibers, Skeletal / Q000737:chemistry / Q000166:cytology / Q000201:enzymology; D009206:Myocardium / Q000737:chemistry / Q000166:cytology / Q000201:enzymology; D009210:Myofibrils / Q000737:chemistry / Q000201:enzymology; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000737:chemistry / Q000201:enzymology; D016019:Survival Analysis; D014421:Turkey; D016277:Ventricular Function, Left