Cardiomegaly induced by pressure overload in newborn rats is accompanied by altered expression of the long isoform of G(s)alpha protein and deranged signaling of adenylyl cyclase.
G proteins-coupled signaling pathways appear to play a role in the development of cardiac hypertrophy and its progression to heart failure. The present study aimed to investigate trimeric G proteins and adenylyl cyclase signaling in immature as well as in adult rat myocardium during this process caused by pressure overload. Pressure overload was induced in newborn (2-day-old) rats by abdominal aortic banding and myocardial preparations from left ventricular myocardium of immature (10-day-old) and adult (90-day-old) animals were analyzed for the relative content of different G protein subunits and adenylyl cyclase (AC) by immunoblotting with specific antibodies. A functional status of the AC signaling system was also evaluated. Normal maturation of rat heart was accompanied by increased expression of AC type V/VI and VII and of the long isoform (G(s)alphaL) of G(s)alpha protein. In parallel, the amounts of myocardial G(i)alpha/G(o)alpha proteins tended to decrease, and G(q)alpha/G(11)alpha and Gbeta did not change. Interestingly, whereas fluoride-stimulated AC activity increased in the course of maturation, activity of AC measured under other experimental conditions (stimulation by Mn2+, forskolin or isoproterenol) was lower in adult than in young rat myocardium. Pressure overload did not influence distribution of G proteins in immature myocardium, but considerably decreased the content of G(s)alphaL and increased G(o)alpha proteins in hearts of 90-day-old rats. These hearts exhibited worsened functional reserve as compared to age-matched controls and activity of AC was also markedly lower. A considerable reduction in Mn(2+)-stimulated AC activity together with similar decrease in AC activity determined under other stimulation conditions suggests that it is a function of AC catalytic subunit that is primarily impaired in this model of pressure overload.
Novotny
Jiri
J
Department of Physiology and Developmental Biology, Faculty of Natural Sciences, Charles University, Prague, Czech Republic. novjiri@biomed.cas.cz
Hrbasová
Markéta
M
Kolár
Frantisek
F
Svoboda
Petr
P
D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism*; D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002316:Cardiotonic Agents / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D005459:Fluorides / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D015870:Gene Expression; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008345:Manganese / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism; D011312:Pressure; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
D002316:Cardiotonic Agents; D020033:Protein Isoforms; D005576:Colforsin; D008345:Manganese; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D005459:Fluorides