Differential changes in beta-adrenoceptor signal transduction in left and right ventricles of infarcted rats.
Although different experimental and clinical studies have revealed varying degrees of defects in beta-adrenoceptors (beta-ARs) during the development of heart failure, the mechanisms for differences in beta-AR signal transduction between the left (LV) and right ventricle (RV) are not understood. Because biochemical alterations in the myocardium depend on the stage of heart disease, this study was undertaken to assess the status of beta-ARs in the LV and RV at different stages of heart failure. Myocardial infarction was induced in rats by occluding the left coronary artery for 8 and 24 weeks. The beta-AR signal transduction was monitored by measuring beta1-AR density, the isoproterenol-induced positive inotropic effect, the increase in [Ca2+]i in cardiomyocytes, and the activation of adenylyl cyclase. The beta-AR signal transduction parameters in the 8- and 24-week failing LV were depressed, whereas the RV showed upregulation at 8 weeks and downregulation at 24 weeks of these mechanisms. These results suggest that beta-AR-mediated signal transduction in the LV and RV are differentially regulated and are dependent upon the stage of development of congestive heart failure due to myocardial infarction.
Sethi
Rajat
R
Irma Lerma Rangel College of Pharmacy, Department of Pharmaceutical Sciences, TX A&M University, TX, USA.
Saini
Harjot K
HK
Wang
Xi
X
Elimban
Vijayan
V
Babick
Andrea
A
Dhalla
Naranjan S
NS
D000262:Adenylyl Cyclases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011869:Radioligand Assay / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D018342:Receptors, Adrenergic, beta-1 / Q000032:analysis / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D018342:Receptors, Adrenergic, beta-1; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D002118:Calcium