BACKGROUND/AIMS: Previously, we found that catecholamine (CA) infusion in rats induced pulmonary injury with edema and inflammation resembling acute lung injury in humans. Here, we examined effects of norepinephrine (NE) and of selective α- and β-adrenergic agonists on the remodeling of pulmonary extracellular matrix. METHODS: Eighty rats were infused over 8-72 h with NE, phenylephrine (PE), isoproterenol (ISO) or NaCl solution. We investigated mRNA expression of collagen, matrix metalloproteinase (MMP)-2, its tissue inhibitor (TIMP-2) and transforming growth factor (TGF)-β isoforms in lung tissue. Additionally, lung histology, hemodynamic function and cardiac hypertrophy were evaluated. RESULTS: After 72 h of infusion, lung histology showed beginning fibrosis and vascular hypertrophy. Collagen type I, MMP-2 and TIMP-2 mRNA expression were significantly elevated. All these effects were most pronounced with NE while PE and ISO induced weaker responses. TGF-β mRNA expression was also elevated after 72 h, predominantly after PE infusion. Cardiac hypertrophy was most pronounced after ISO infusion. CONCLUSION: CA infusion over 72 h may induce pulmonary remodeling. Mainly α-adrenergic but also β-adrenergic mechanisms contribute to these processes. In contrast, cardiac hypertrophy is predominantly mediated by β-adrenergic stimulation and hence, is considered to be a direct adrenergic effect rather than a consequence of pulmonary fibrosis.
BACKGROUND/AIMS: Previously, we found that catecholamine (CA) infusion in rats induced pulmonary injury with edema and inflammation resembling acute lung injury in humans. Here, we examined effects of norepinephrine (NE) and of selective α- and β-adrenergic agonists on the remodeling of pulmonary extracellular matrix. METHODS: Eighty rats were infused over 8-72 h with NE, phenylephrine (PE), isoproterenol (ISO) or NaCl solution. We investigated mRNA expression of collagen, matrix metalloproteinase (MMP)-2, its tissue inhibitor (TIMP-2) and transforming growth factor (TGF)-β isoforms in lung tissue. Additionally, lung histology, hemodynamic function and cardiac hypertrophy were evaluated. RESULTS: After 72 h of infusion, lung histology showed beginning fibrosis and vascular hypertrophy. Collagen type I, MMP-2 and TIMP-2 mRNA expression were significantly elevated. All these effects were most pronounced with NE while PE and ISO induced weaker responses. TGF-β mRNA expression was also elevated after 72 h, predominantly after PE infusion. Cardiac hypertrophy was most pronounced after ISO infusion. CONCLUSION: CA infusion over 72 h may induce pulmonary remodeling. Mainly α-adrenergic but also β-adrenergic mechanisms contribute to these processes. In contrast, cardiac hypertrophy is predominantly mediated by β-adrenergic stimulation and hence, is considered to be a direct adrenergic effect rather than a consequence of pulmonary fibrosis.
Authors: Ruijuan Gao; Xueyan Peng; Carrighan Perry; Huanxing Sun; Aglaia Ntokou; Changwan Ryu; Jose L Gomez; Benjamin C Reeves; Anjali Walia; Naftali Kaminski; Nir Neumark; Genta Ishikawa; Katharine E Black; Lida P Hariri; Meagan W Moore; Mridu Gulati; Robert J Homer; Daniel M Greif; Holger K Eltzschig; Erica L Herzog Journal: J Clin Invest Date: 2021-01-04 Impact factor: 14.808