title: Effects of beta3-adrenoceptor activation on the interaction between adrenoceptors and angiotensin II receptors in apolipoprotein E knockout mouse lung.
abstract: 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.
authors.affiliation: Department of Emergency, Beijing Anzhen Hospital, Capital Medical University, 100029 Beijing, China; Beijing Institute of Heart Lung and Blood Vessel Diseases, 100029 Beijing, China.
authors.forename: Zhi-li
authors.initials: ZL
authors.lastname: Jiang
authors.affiliation: Department of Emergency, Beijing Anzhen Hospital, Capital Medical University, 100029 Beijing, China; Beijing Institute of Heart Lung and Blood Vessel Diseases, 100029 Beijing, China. Electronic address: jiangzhilitg@sohu.com.
authors.forename: Yan-fang
authors.initials: YF
authors.lastname: Li
authors.affiliation: Department of Emergency, Beijing Anzhen Hospital, Capital Medical University, 100029 Beijing, China; Beijing Institute of Heart Lung and Blood Vessel Diseases, 100029 Beijing, China.
authors.forename: Jun-ying
authors.initials: JY
authors.lastname: Song
authors.affiliation: Department of Emergency, Beijing Anzhen Hospital, Capital Medical University, 100029 Beijing, China; Beijing Institute of Heart Lung and Blood Vessel Diseases, 100029 Beijing, China.
authors.forename: Yan-qing
authors.initials: YQ
authors.lastname: Guo
mesh_terms: D058667:Adrenergic beta-3 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology; D058673:Adrenergic beta-3 Receptor Antagonists / Q000494:pharmacology; D000375:Aging / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D006949:Hyperlipidemias / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism; D011941:Receptors, Adrenergic / Q000235:genetics / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics / Q000378:metabolism*; D011945:Receptors, Angiotensin / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists; D058673:Adrenergic beta-3 Receptor Antagonists; D001057:Apolipoproteins E; D008078:Cholesterol, LDL; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011941:Receptors, Adrenergic; D022702:Receptors, Adrenergic, beta-3; D011945:Receptors, Angiotensin; D014280:Triglycerides; D002784:Cholesterol
keywords: Angiotensin receptor; Apolipoprotein E knockout; Beta3 adrenoceptor; Interaction