Angiotensin Type 2 Receptors Are Reexpressed by Cardiac Fibroblasts From Failing Myopathic Hamster Hearts and Inhibit Cell Growth and Fibrillar Collagen Metabolism

摘要: Background Angiotensin (Ang) II type 1 receptor (AT1-R) induces cardiomyocyte hypertrophy and fibroblast proliferation, whereas the physiological role of AT2-R in cardiac remodeling remains poorly defined. Methods Results Using Bio14.6 cardiomyopathic (CM) hamsters, we found that sites were increased by 153% during heart failure compared with F1B controls. AT1-R numbers 72% stage then decreased to control level failure. Such differential regulation was consistent changes respective mRNA levels. Autoradiography immunocytochemistry revealed both are localized at higher densities fibroblasts present fibrous regions. Surrounding myocardium predominantly expressed AT1-R, but expression less than Cardiac isolated from CM hearts not hamsters (30 fmol/mg protein). expressing AT2-R, Ang stimulated net collagenous protein production 48% pretreatment an antagonist, PD123319, evoked a further elevation (83%). II–induced synthesis fibronectin collagen I enhanced 40% 53%, respectively, PD123319. DNA (assessed [3H]thymidine uptake) significantly agonist CGP42112A reduced serum-stimulated increase cell 23%. Treatment TCV116, for 20 weeks inhibited progression interstitial fibrosis 28%, 44-week PD123319 treatment 20-week treatment, extent region significantly, 29%. Conclusions These findings demonstrate is reexpressed regions failing exerts anti–AT1-R action on inhibiting fibrillar metabolism growth fibroblasts.