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

• Published in: Current vascular pharmacology Vol. 15; no. 3; p. 265
• Main Authors: Souza Bomfim, Guilherme Henrique, Mendez-Lopez, Iago, Arranz-Tagarro, Juan Alberto, Ferraz Carbonel, Adriana Aparecida, Roman-Campos, Danilo, Padín, Juan Fernando, Garcia, Antonio Garcia, Jurkiewicz, Aron, Jurkiewicz, Neide Hyppolito
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01.01.2017
• Subjects: Alcohol Drinking - adverse effects; Animals; Aorta, Thoracic - metabolism; Aorta, Thoracic - physiopathology; Blood Pressure; Calcium - metabolism; Calcium Signaling; Disease Models, Animal; Endoplasmic Reticulum - metabolism; Ethanol; Hypertension - etiology; Hypertension - metabolism; Hypertension - physiopathology; Male; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - physiopathology; Myocytes, Cardiac - metabolism; Myocytes, Smooth Muscle - metabolism; ORAI1 Protein - metabolism; Rats, Inbred SHR; Rats, Inbred WKY; Stromal Interaction Molecule 1 - metabolism; Time Factors; Up-Regulation; Vascular Remodeling; Vasoconstriction; STIM-1/Orai-1-mediated SOCCs activation; hypertension development; aortic remodeling; cardiac hypertrophy; chronic EtOH consumption; Ca2+ handling
• ISSN: 1875-6212
• DOI: 10.2174/1570161115666170201122750

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. 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. 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. 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.