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 β3-adrenoceptor agonist can improve lipid metabolism disorders. In this study, we aim to investigate the effects of β3-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 β3-adrenoceptor agonist and β3-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 α1A-, α1B-, α2A-, β1-, β2-, β3-adrenoceptors and angiotensin II type 1 and type 2 receptors in lung. We found that β3-adrenoceptor agonist could decrease TG, TC and LDL-C in aged ApoE(-/-) mice (P<0.01) and down-regulate the expressions of α1A-, α2A-adrenoceptors and angiotensin II type 1 receptor which were significantly increased in model mice (P<0.01, P<0.05). Compared with model mice, α1B-, β1-, β2-, β3-adrenoceptors and angiotensin II type 2 receptor expressions were increased in β3-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 β3-adrenoceptor agonist, which shows there are interactions between β3-adrenoceptor and other adrenoceptor subtypes and angiotensin II receptors. These interactions may play a protective role in lung under condition of hyperlipidemia.