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Sex differences in vascular expression and activation of STIM‐1/Orai‐1 during hypertension: focus on calcium regulation
Author(s) -
Giachini Fernanda,
Carneiro Fernando S,
Lima Victor V,
Carneiro Zidonia N,
Dorrance Anne,
Tostes Rita C,
Webb R. Clinton
Publication year - 2009
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/fasebj.23.1_supplement.781.15
Subject(s) - endocrinology , thapsigargin , medicine , contraction (grammar) , endoplasmic reticulum , orai1 , intracellular , chemistry , calcium , aorta , stim1 , voltage dependent calcium channel , microbiology and biotechnology , biology
Sex‐related differences in Ca 2+ ‐dependent signaling contributes to greater contractile‐responses in male hypertensive rats. We hypothesized that vascular protection in females reflects differences in Ca 2+ mobilization due to differential activation of CRAC (Ca 2+ release‐activated Ca 2+ ) channels through Orai1, via its interaction with the intracellular Ca 2+ sensor STIM‐1 (stromal interaction molecules). Endothelium‐denuded aortic rings from male and female stroke prone spontaneously hypertensive rats (SHRSP) and Wistar‐Kyoto (WKY) rats were used to functionally evaluate Ca 2+ influx‐induced contraction. Sarcoplasmic reticulum Ca +2 ATPase was inhibited with thapsigargin (10uM). During the Ca 2+ loading period: (1) force development was augmented in aortas from male SHRSP (10.0±0.9mN, n=6) vs. female (7.5±1.1mN, n=6); (2) CRAC channel blockade with 2‐APB and Gd 3+ as well as (3) neutralizing antibodies against STIM‐1 and Orai‐1 normalized differences in contraction between aortas from male and female SHRSP. Expression of Orai‐1 and STIM‐1 proteins was increased in aorta from male SHRSP, vs. female SHRSP or WKY. Augmented activation of STIM‐1/Orai‐1 in aorta from male SHRSP may represent a mechanism that contributes to sex‐related impaired control of intracellular Ca 2+ levels. Financial support: NIH ‐ HL71138 and HL74167