Phospholipase C may be involved in norepinephrine-induced cardiac hypertrophy

• Published in: Biochemical and biophysical research communications Vol. 320; no. 3; pp. 1015 - 1019
• Main Authors: Singal, Tushi, Dhalla, Naranjan S, Tappia, Paramjit S
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30.07.2004
• Subjects: Adult cardiomyocytes; Animals; Atrial Natriuretic Factor - drug effects; Atrial Natriuretic Factor - metabolism; Cardiomegaly - chemically induced; Cardiomegaly - metabolism; Cells, Cultured; Dose-Response Relationship, Drug; Heart Ventricles - drug effects; Heart Ventricles - metabolism; Male; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Norepinephrine; Norepinephrine - pharmacology; Phospholipase C; Prazosin; Protein synthesis; Rats; Rats, Sprague-Dawley; Type C Phospholipases - metabolism; α-Adrenoceptors; α-Adrenoceptors; Prazosin; Norepinephrine; Adult cardiomyocytes; Protein synthesis; Phospholipase C
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2004.06.052

Cardiac hypertrophy is characterized by increased cardiomyocyte size, mRNA levels for atrial natriuretic factor (ANF), and protein synthesis. Although activation of the phosphoinositide-specific phospholipase C (PLC) leads to the generation of diacylglycerol (DAG) and inositol 1,4,5-trisphosphate, the involvement of PLC in hypertrophic response remains to be fully understood. The present study was therefore undertaken to examine if the inhibition of PLC activity is associated with a decrease in ANF expression and protein synthesis in cardiomyocytes, due to norepinephrine (NE), a known hypertrophic agent. NE resulted in an increase in ANF gene expression and protein synthesis in adult rat cardiomyocytes, these effects of NE were attenuated by a PLC inhibitor, U73122. The NE-induced increase in ANF gene expression and protein synthesis was also inhibited by an α-adrenoceptor blocker, prazosin. Both U73122 and prazosin depressed the NE-induced increase in DAG production in cardiomyocytes. These results indicate that the α-adrenoceptor mediated PLC activation may be involved in the process of NE-induced cardiac hypertrophy.