Early sequence of cardiac adaptations and growth factor formation in pressure- and volume-overload hypertrophy

To investigate the time sequence of cardiac growth factor formation, echoca rdiographic and hemodynamic measurements were performed at scheduled times, and mRNAs for angiotensinogen, prepro-endothelin-1 (ppET-1), and insulin-l ike growth factor I (IGF-I) were quantified with RT-PCR and localized with in situ hybridization in pigs (fluothane anesthesia) by use of pressure or volume overload (aortic banding and aorta-cava fistula, respectively). Rela tive peptide formation was also measured by radioimmunoassay. In pressure o verload, angiotensinogen and ppET-1 mRNA overexpression on myocytes (13 tim es vs. sham at 3 h and 112 times at 6 h, respectively) was followed by reco very (12 h) of initially decreased (0.5-6 h) myocardial contractility. In v olume overload, contractility was not decreased, the angiotensinogen gene w as slightly upregulated at 6 h (6.7 times), and ppET-1 was not overexpresse d. IGF-I mRNA was overexpressed on myocytes (at 24 h) in both volume and pr essure overload (14 times and 37 times, respectively). In the latter settin g, a second ppET-1 overexpression was detectable on myocytes at 7 days. In conclusion, acute cardiac adaptation responses involve different growth fac tor activation over time in pressure versus volume overload; growth factors initially support myocardial contractility and thereafter induce myocardia l hypertrophy.