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Caveolae regulate vasoconstriction of conduit arteries to angiotensin II in hindlimb unweighted rats
Author(s) -
Wang Zhongchao,
Bai Yungang,
Yu Jinwen,
Liu Huan,
Cheng Yaoping,
Liu Yonghong,
Xie Xiaoping,
Ma Jin,
Bao Junxiang
Publication year - 2015
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp270823
Subject(s) - vasoconstriction , caveolae , weightlessness , medicine , angiotensin ii , vascular smooth muscle , isometric exercise , endocrinology , chemistry , hindlimb , orthostatic intolerance , aorta , anatomy , orthostatic vital signs , receptor , blood pressure , cell , biochemistry , smooth muscle , physics , astronomy
Key points Exposure to microgravity induces postflight orthostatic intolerance on re‐exposure to 1 G gravity which is second to the structural and functional remodelling of arteries. We found the maximal developed force ( E max ) of angiotensin II‐elicited vasoconstriction was decreased in abdominal aorta, unchanged in thoracic aorta and increased in carotid artery by simulated weightlessness. However, the sensitivity of the response (EC 50 ) was decreased in all of the arteries as was the desensitization of angiotensin II type I receptor (AT 1 ) upon angiotensin II stimulation. We demonstrate that caveolae on vascular smooth muscle cells play a key role in the adaptation of EC 50 and AT 1 desensitization, but not E max of the response to simulated weightlessness. This study gives insight into the mechanism underlying the arterial functional remodelling during weightlessness. Further, the findings might stimulate new ideas for research into countermeasures to postflight orthostatic intolerance upon astronauts returning to the earth.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 (AT 1 ) 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 EC 50 of the response was increased in all three arteries ( P < 0.05). AT 1 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 AT 1 and cav‐1 significantly in control but not HU arteries. Both the number of caveolae and the binding of AT 1 and cav‐1 in HU arteries were restored by cholesterol pretreatment which also reinstated the change in EC 50 as well as the level of AT 1 desensitization. These results indicate that modified caveolae in vascular smooth muscle cells could interfere with the binding of AT 1 and cav‐1 mediating the adaptation of Ang II‐elicited vasoconstriction to HU.