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.