Effects of beta3-adrenoceptor activation on the interaction between adrenoceptors and angiotensin II receptors in apolipoprotein E knockout mouse lung.

Hyperlipidemia can be harmful to the lung and β 3 -adrenoceptor agonist can improve lipid metabolism disorders. In this study, we aim to investigate the effects of β 3 -adrenoceptor activation on the interactions of adrenoceptors and angiotensin II receptors in aged apolipoprotein E gene knockout (ApoE −/− ) mouse lung. Ten wild type C57BL/6J mice were included as normal control, 40 ApoE −/− mice were randomly divided into hyperlipidemia model (saline), low dose and high dose β 3 -adrenoceptor agonist and β 3 -adrenoceptor antagonist groups. After 26 weeks of high-fat diet, treatments were given for 12 weeks. Total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) were examined by an automatic biochemical analyzer. Quantitative real-time PCR and Western blot were used to analyze the mRNA and protein expression of α 1A -, α 1B -, α 2A -, β 1 -, β 2 -, β 3 -adrenoceptors and angiotensin II type 1 and type 2 receptors in lung. We found that β 3 -adrenoceptor agonist could decrease TG, TC and LDL-C in aged ApoE −/− mice ( P <0.01) and down-regulate the expressions of α 1A -, α 2A -adrenoceptors and angiotensin II type 1 receptor which were significantly increased in model mice ( P <0.01, P <0.05). Compared with model mice, α 1B -, β 1 -, β 2 -, β 3 -adrenoceptors and angiotensin II type 2 receptor expressions were increased in β 3 -adrenoceptor agonist-treat mice ( P <0.01, P <0.05). These findings suggest that the expressions of adrenoceptors and angiotensin II receptors in lung are regulated towards adverse directions after taking β 3 -adrenoceptor agonist, which shows there are interactions between β 3 -adrenoceptor and other adrenoceptor subtypes and angiotensin II receptors. These interactions may play a protective role in lung under condition of hyperlipidemia. [ABSTRACT FROM AUTHOR]