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Functional Upregulation of STIM-1/Orai-1-Mediated Store-Operated Ca2+ Contributing to the Hypertension Development Elicited by Chronic EtOH Consumption

[ Vol. 15 , Issue. 3 ]

Author(s):

Guilherme Henrique Souza Bomfim*, Iago Mendez-Lopez, Juan Alberto Arranz-Tagarro, Adriana Aparecida Ferraz Carbonel, Danilo Roman-Campos, Juan Fernando Padín, Antonio Garcia Garcia, Aron Jurkiewicz and Neide Hyppolito Jurkiewicz*   Pages 265 - 281 ( 17 )

Abstract:


Background: Chronic ethanol (EtOH) consumption has been associated with deleterious effects on the cardiovascular system by abnormal calcium (Ca2+) handling. Store-operated Ca2+ entry (SOCE) is related to cardiovascular remodeling which leads to the hypertension development, and the coupling between STIM-1 (ER Ca2+ sensor) and Orai-1 (channel pore) is a key mechanism to control SOCE through of store-operated Ca2+ channels (SOCCs). However, the role of STIM-1/Orai-1-mediated SOCE and its cross-talk with EtOH-triggered vascular remodeling and hypertension remain poorly understood. We address this subject in the present study by evaluating how chronic EtOH consumption induces alterations in Ca2+ handling via SOCE. <p></p> Methods: Male Wistar Kyoto (WKY) and Spontaneously Hypertensive (SHR) rats were subjected to the intake of increasing EtOH concentrations (5-20%, for 30 days). Systolic blood pressure (SBP) and EtOH concentration were measured; cardiovascular remodeling was assessed by histomorphometry; and function/ expression of STIM-1/Orai-1-mediated Ca2+ influx were evaluated by isometric contraction and western blot experiments. <p></p> Results: Compared to the WKY-Control, our results show that: (1) chronic EtOH consumption caused a significant elevation of SBP in both strains; (2) cardiac hypertrophy and hypertrophic aortic wall remodeling much more pronounced in WKY-EtOH; (3) decreased capacity of ER to store and release Ca2+; (4) increased STIM-1/Orai-1-mediated SOCCs activation, which was selectively inhibited by YM-58483; and (5) increased expression of STIM-1 in WKY-EtOH and SHR-Control rats. <p></p> Conclusion: These findings suggest that hypertrophic aortic remodeling and abnormal contraction triggered mainly by Ca2+ overload via STIM-1/Orai-1-mediated SOCE through SOCCs are involved hypertension developed by EtOH consumption. <p></p>

Keywords:

Ca2+ handling, STIM-1/Orai-1-mediated SOCCs activation, cardiac hypertrophy, aortic remodeling, chronic EtOH consumption, hypertension development.

Affiliation:

Departamento de Farmacologia, Escola Paulista de Medicina da Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Instituto Teófilo Hernando de I+D del Medicamento, Facultad de Medicina de la Universidad Autónoma de Madrid (UAM), Madrid, Instituto Teófilo Hernando de I+D del Medicamento, Facultad de Medicina de la Universidad Autónoma de Madrid (UAM), Madrid, Departamento de Morfologia e Genetica, Escola Paulista de Medicina da Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Departamento de Biofísica, Escola Paulista de Medicina da Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Instituto Teófilo Hernando de I+D del Medicamento, Facultad de Medicina de la Universidad Autónoma de Madrid (UAM), Madrid, Instituto Teófilo Hernando de I+D del Medicamento, Facultad de Medicina de la Universidad Autónoma de Madrid (UAM), Madrid, Departamento de Farmacologia, Escola Paulista de Medicina da Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Rua tres de Maio n° 100, 04044-020. Sao Paulo-SP

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