title: Phospholipase C may be involved in norepinephrine-induced cardiac hypertrophy.
abstract: 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 alpha-adrenoceptor blocker, prazosin. Both U73122 and prazosin depressed the NE-induced increase in DAG production in cardiomyocytes. These results indicate that the alpha-adrenoceptor mediated PLC activation may be involved in the process of NE-induced cardiac hypertrophy.
authors.affiliation: Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre, University of Manitoba, Winnipeg, Canada.
authors.forename: Tushi
authors.initials: T
authors.lastname: Singal
authors.forename: Naranjan S
authors.initials: NS
authors.lastname: Dhalla
authors.forename: Paramjit S
authors.initials: PS
authors.lastname: Tappia
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000187:drug effects / Q000378:metabolism*; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D010738:Type C Phospholipases / Q000378:metabolism*
chemical_list: D009320:Atrial Natriuretic Factor; D010738:Type C Phospholipases; D009638:Norepinephrine