title: Caveolae regulate vasoconstriction of conduit arteries to angiotensin II in hindlimb unweighted rats.
abstract: Weightlessness induces the functional remodelling of arteries, but the changes to angiotensin II (Ang II)-elicited vasoconstriction and the underlying mechanism have never been reported. Caveolae are invaginations of the cell membrane crucial for the contraction of vascular smooth muscle cells, so we investigated the adaptation of Ang II-elicited vasoconstriction to simulated weightlessness and the role of caveolae in it. The 4 week hindlimb unweighted (HU) rat was used to simulate the effects of weightlessness. Ang II-elicited vasoconstriction was measured by isometric force recording. The morphology of caveolae was examined by transmission electron microscope. The binding of the angiotensin II type 1 receptor (AT1 ) and caveolin-1 (cav-1) was examined by coimmunoprecipitation and Western blot. We found that the maximal developing force (E(max)) of Ang II-elicited vasoconstriction was decreased in abdominal aorta by 30.6%, unchanged in thoracic aorta and increased in carotid artery by 17.9% after HU, while EC50 of the response was increased in all three arteries (P < 0.05). AT1 desensitization upon activation was significantly reduced by HU in all three arteries, as was the number of caveolae (P < 0.05). Furthermore, Ang II promoted the binding of AT1 and cav-1 significantly in control but not HU arteries. Both the number of caveolae and the binding of AT1 and cav-1 in HU arteries were restored by cholesterol pretreatment which also reinstated the change in EC50 as well as the level of AT1 desensitization. These results indicate that modified caveolae in vascular smooth muscle cells could interfere with the binding of AT1 and cav-1 mediating the adaptation of Ang II-elicited vasoconstriction to HU.
authors.affiliation: Department of Aerospace Physiology, Fourth Military Medical University, Xi'an, 710032, P. R. China.
authors.forename: Zhongchao
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Aerospace Physiology, Fourth Military Medical University, Xi'an, 710032, P. R. China.
authors.forename: Yungang
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Aerospace Physiology, Fourth Military Medical University, Xi'an, 710032, P. R. China.
authors.forename: Jinwen
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Aerospace Physiology, Fourth Military Medical University, Xi'an, 710032, P. R. China.
authors.forename: Huan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Aerospace Hygiene, Fourth Military Medical University, Xi'an, 710032, P. R. China.
authors.forename: Yaoping
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Neurology, Xi Jing Hospital, Fourth Military Medical University, Xi'an, 710032, P. R. China.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Aerospace Hygiene, Fourth Military Medical University, Xi'an, 710032, P. R. China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Aerospace Physiology, Fourth Military Medical University, Xi'an, 710032, P. R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Aerospace Hygiene, Fourth Military Medical University, Xi'an, 710032, P. R. China.
authors.forename: Junxiang
authors.initials: J
authors.lastname: Bao
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000502:physiology*; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology*; D002339:Carotid Arteries / Q000187:drug effects / Q000502:physiology*; D021941:Caveolae / Q000502:physiology*; D051242:Caveolin 1 / Q000378:metabolism; D002784:Cholesterol / Q000494:pharmacology; D006614:Hindlimb; D019417:Hindlimb Suspension / Q000502:physiology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014893:Weightlessness
chemical_list: D051242:Caveolin 1; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D002784:Cholesterol