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BK Ca compensates impaired coronary vasoreactivity through RhoA/ROCK pathway in hind‐limb unweighted rats
Author(s) -
Wu Yue,
Yue Zhijie,
Wang Qiguang,
Lv Qiang,
Liu Huan,
Bai Yungang,
Li Shaohua,
Xie Manjiang,
Bao Junxiang,
Ma Jin,
Wang Zhongchao,
Zhu Xianyang
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201901273r
Subject(s) - rhoa , vasoconstriction , rho associated protein kinase , chemistry , myosin light chain phosphatase , bk channel , vascular smooth muscle , medicine , endocrinology , phosphorylation , anatomy , signal transduction , potassium channel , biochemistry , smooth muscle
Previous studies have demonstrated cardiac and vascular remodeling induced by microgravity exposure. Yet, as the most important branch of vasculatures circulating the heart, the coronary artery has been seldomly studied about its adaptations under microgravity conditions. Large‐conductance Ca 2+ ‐activated potassium channel (BK Ca ) and the Ras homolog family member A (RhoA)/Rho kinase (ROCK) pathway play key roles in control of vascular tone and mediation of microgravity‐induced vascular adjustments. Therefore, we investigated the adaptation of coronary vasoreactivity to simulated microgravity and the role of BK Ca and the RhoA/ROCK pathway in it. Four‐week‐old hind‐limb unweighted (HU) rats were adopted to simulate effects of microgravity. Right coronary artery (RCA) constriction was measured by isometric force recording. The activity and expression of BK Ca and the RhoA/ROCK pathway were examined by Western blot, patch‐clamp recordings, and immunoprecipitation. We found HU significantly decreased RCA vasoconstriction to KCl, serotonin, and U‐46619, but increased protein expression and current densities of BK Ca , inhibition of which by iberiotoxin (IBTX) further decreased RCA vasoconstriction ( P < 0.05). Expression of RhoA and ROCK as well as active RhoA and phosphorylation of myosin light chain (MLC) at Ser 19 and MLC phosphatase target‐1 at Thr 696 were significantly increased by HU, and ROCK inhibitor Y‐27632 exerted greater suppressing effect on HU RCA vasoconstriction than that of control ( P < 0.05). BK Ca opener NS1619 increased HU RCA vasoconstriction, which was blocked by both RhoA and ROCK inhibitor, similar to the effect of IBTX. These results indicate that HU impairs coronary vasoconstriction but enhances BK Ca activity acting as a protective mechanism avoiding excessive decrease of coronary vasoreactivity through activation of the RhoA/ROCK pathway.—Wu, Y., Yue, Z., Wang Q., Lv, Q., Liu, H., Bai, Y. Li S. Xie M. Bao J. Ma J. Zhu X. Wang Z. BK Ca compensates impaired coronary vasoreactivity through RhoA/ROCK pathway in hind‐limb unweighted rats. FASEB J. 33, 13358–13366 (2019). www.fasebj.org