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

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

Volume: 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*

Affiliation:

• Departamento de Farmacologia, Escola Paulista de Medicina da Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo,Brazil

• Rua tres de Maio n° 100, 04044-020. Sao Paulo-SP,Brazil

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

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.

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.

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.

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.

Cite this article as:

Souza Bomfim Henrique Guilherme*, Mendez-Lopez Iago, Arranz-Tagarro Alberto Juan, Ferraz Carbonel Aparecida Adriana, Roman-Campos Danilo, Padín Fernando Juan, Garcia Garcia Antonio, Jurkiewicz Aron and Jurkiewicz Hyppolito Neide*, Functional Upregulation of STIM-1/Orai-1-Mediated Store-Operated Ca2+ Contributing to the Hypertension Development Elicited by Chronic EtOH Consumption, Current Vascular Pharmacology 2017; 15 (3) . https://dx.doi.org/10.2174/1570161115666170201122750

DOI https://dx.doi.org/10.2174/1570161115666170201122750	Print ISSN 1570-1611
Publisher Name Bentham Science Publisher	Online ISSN 1875-6212