STIM1/Orai1 contributes to sex differences in vascular responses to calcium in spontaneously hypertensive rats

Fernanda R.C. Giachini, Victor V. Lima, Fernando P. Filgueira, Anne M. Dorrance, Maria Helena C. Carvalho, Zuleica B. Fortes, R. Clinton Webb, Rita C. Tostes

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Sex differences in Ca 2+ -dependent signalling and homoeostasis in the vasculature of hypertensive rats are well characterized. However, sex-related differences in SOCE (store-operated Ca 2+ entry) have been minimally investigated. We hypothesized that vascular protection in females, compared with males, reflects decreased Ca 2+ mobilization due to diminished activation of Orai1/STIM1 (stromal interaction molecule 1). In addition, we investigated whether ovariectomy in females affects the activation of the Orai1/STIM1 pathway. Endothelium-denuded aortic rings from male and female SHRSP (stroke-prone spontaneously hypertensive rats) and WKY (Wistar-Kyoto) rats and from OVX (ovariectomized) or sham female SHRSP and WKY rats were used to functionally evaluate Ca 2+ influx-induced contractions. Compared with females, aorta from male SHRSP displayed: (i) increased contraction during the Ca 2+ -loading period; (ii) similar transient contraction during Ca 2+ release from the intracellular stores; (iii) increased activation of STIM1 and Orai1, as shown by the blockade of STIM1 and Orai1 with neutralizing antibodies, which reversed the sex differences in contraction during the Ca 2+-loading period; and (iv) increased expression of STIM1 and Orai1. Additionally, we found that aortas fromOVX-SHRSP showed increased contraction during the Ca 2+ -loading period and increased Orai1 expression, but no changes in the SR (sarcoplasmic reticulum)-buffering capacity or STIM1 expression. These findings suggest that augmented activation of STIM1/Orai1 in aortas from male SHRSP represents a mechanism that contributes to sex-related impaired control of intracellular Ca 2+ levels. Furthermore, female sex hormones may negatively modulate the STIM/Orai1 pathway, contributing to vascular protection observed in female rats.

Original languageEnglish (US)
Pages (from-to)215-226
Number of pages12
JournalClinical Science
Volume122
Issue number5
DOIs
StatePublished - Mar 2012

Keywords

  • Aorta
  • Calcium
  • Hypertension
  • Orai1
  • Sex difference
  • Stromal interaction molecule 1 (STIM1)
  • Vascular protection

ASJC Scopus subject areas

  • Medicine(all)

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    Giachini, F. R. C., Lima, V. V., Filgueira, F. P., Dorrance, A. M., Carvalho, M. H. C., Fortes, Z. B., Webb, R. C., & Tostes, R. C. (2012). STIM1/Orai1 contributes to sex differences in vascular responses to calcium in spontaneously hypertensive rats. Clinical Science, 122(5), 215-226. https://doi.org/10.1042/CS20110312