Dependence of changes in beta-adrenoceptor signal transduction on type and stage of cardiac hypertrophy

• Published in: Journal of applied physiology (1985) 2007-03, Vol.102 (3), p.978-984
• Main Authors: Sethi, Rajat, Saini, Harjot K, Guo, Xiaobing, Wang, Xi, Elimban, Vijayan, Dhalla, Naranjan S
• Format: Article
• Language: English
• Subjects: Adenylyl Cyclases - metabolism; Animals; Biological and medical sciences; Calcium - metabolism; Cardiomegaly - metabolism; Cardiomegaly - physiopathology; Cardiotonic Agents; Fundamental and applied biological sciences. Psychology; Isoproterenol; Male; Myocytes, Cardiac - metabolism; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, beta - metabolism; Signal Transduction - physiology; Ventricular Function, Left - physiology
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.00921.2006

1 Irma Lerma Rangel College of Pharmacy, Department of Pharmaceutical Sciences, Texas A & M University Health Sciences Center, Kingsville, Texas; and 2 Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre and Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada Submitted 21 August 2006 ; accepted in final form 16 November 2006 To examine whether cardiac hypertrophy is associated with changes in -adrenoceptor signal transduction mechanisms, pressure overload (PO) was induced by occlusion of the abdominal aorta and volume overload (VO) by creation of an aortocaval shunt for 4 and 24 wk in rats. After hemodynamic assessment of the animals, the left ventricular (LV) particulate fraction was isolated for measurement of 1 -adrenoceptors and adenylyl cyclase activity, and cardiomyocytes were isolated for monitoring of the intracellular Ca 2+ concentration. Although PO and VO produced cardiac hypertrophy and increased LV end-diastolic pressure at 4 wk, cardiac function was increased in animals subjected to PO but remained unaltered in animals subjected to VO. Cardiac hypertrophy and increased LV end-diastolic pressure were associated with depressed cardiac function at 24 wk of PO or VO, but clinical signs of congestive heart failure were evident only in animals subjected to VO. Isoproterenol-induced increases in cardiac function, activation of adenylyl cyclase activity, and increase in intracellular Ca 2+ concentration, as well as 1 -adrenoceptor density, were unaltered by PO at 4 wk, augmented by VO at 4 wk, and attenuated by PO and VO at 24 wk. These results suggest that alterations in 1 -adrenoceptor signal transduction are dependent on the type and stage of cardiac hypertrophy. pressure overload; volume overload; cardiac function; -adrenoceptors; adenylyl cyclase; intracellular calcium concentration Address for reprint requests and other correspondence: N. S. Dhalla, Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, 351 Tache Ave., Winnipeg, MB, Canada R2H 2A6 (e-mail: nsdhalla{at}sbrc.ca )