X Sun1, Y C Ng. 1. Department of Pharmacology, College of Medicine, Pennsylvania State University, Hershey 17033, USA.
Abstract
OBJECTIVES: The effects of norepinephrine on expression of cardiac genes during pathological cardiac growth and heart failure are not fully understood. Tissue insulin-like growth factor 1 (IGF-1) and its receptor (IGF-1R) play an important role in the regulation of the hyperplastic capacity of cardiac myocytes. Sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2), on the other hand, is important in regulating cardiac contractile function. The present study examined the effects of elevated levels of NE on expression of IGF-1/IGF-1R and SERCA2 mRNAs. METHODS: Rats were infused with NE using osmotic minipumps for 3 and 6 days at a rate of 50 micrograms/kg/h and also at a higher dose (130 micrograms/kg/h) for 6 and 14 days. Levels of expression of IGF-1/IGF-1R and SERCA2 mRNAs were determined by ribonuclease protection assay and by Northern blotting, respectively. RESULTS: NE treatment significantly increased IGF-1 mRNA levels in both left- and right-ventricle; however, levels of IGF-1R increased in the left- but not the right-ventricle. By contrast, NE infusion at both the lower dose and the higher dose failed to alter expression of SERCA2 mRNA. CONCLUSION: Our results suggest that NE treatment differentially regulates expression of IGF-1 and IGF-1R in the ventricles of rat heart and that NE appears not to affect expression of SERCA2 mRNA.
OBJECTIVES: The effects of norepinephrine on expression of cardiac genes during pathological cardiac growth and heart failure are not fully understood. Tissue insulin-like growth factor 1 (IGF-1) and its receptor (IGF-1R) play an important role in the regulation of the hyperplastic capacity of cardiac myocytes. Sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2), on the other hand, is important in regulating cardiac contractile function. The present study examined the effects of elevated levels of NE on expression of IGF-1/IGF-1R and SERCA2 mRNAs. METHODS:Rats were infused with NE using osmotic minipumps for 3 and 6 days at a rate of 50 micrograms/kg/h and also at a higher dose (130 micrograms/kg/h) for 6 and 14 days. Levels of expression of IGF-1/IGF-1R and SERCA2 mRNAs were determined by ribonuclease protection assay and by Northern blotting, respectively. RESULTS: NE treatment significantly increased IGF-1 mRNA levels in both left- and right-ventricle; however, levels of IGF-1R increased in the left- but not the right-ventricle. By contrast, NE infusion at both the lower dose and the higher dose failed to alter expression of SERCA2 mRNA. CONCLUSION: Our results suggest that NE treatment differentially regulates expression of IGF-1 and IGF-1R in the ventricles of rat heart and that NE appears not to affect expression of SERCA2 mRNA.