STIM 1/Orai 1 contributes to sex differences in vascular responses to calcium in spontaneously hypertensive rats

Autor(es)

Giachini, Fernanda R. C. ^[1] ; Lima, Victor V. ^[2] ; Filgueira, Fernando P. ^[3] ; Dorrance, Anne M. ^[4] ; Carvalho, Maria Helena C. ^[5] ; Fortes, Zuleica B. ^[6] ; Webb, R. Clinton ^[7] ; Tostes, Rita C. ^[8]

Afiliação do(s) autor(es)

^[1] Georgia Hlth Sci Univ. Dept Physiol

^[2] Georgia Hlth Sci Univ. Dept Physiol

^[3] Univ Sao Paulo. Dept Pharmacol

^[4] Michigan State Univ. Dept Pharmacol & Toxicol

^[5] Univ Sao Paulo. Dept Pharmacol

^[6] Univ Sao Paulo. Dept Pharmacol

^[7] Georgia Hlth Sci Univ. Dept Physiol

^[8] Georgia Hlth Sci Univ. Dept Physiol

• Tipo de documento: Artigo Científico
• Fonte: Clinical Science; v. 122, n. 5-6, p. 215-226, MAR 2012.
• Citações Web of Science: 15

Resumo

Sex differences in Ca2+-dependent signalling and homoeostasis in the vasculature of hypertensive rats are well characterized. However, sex-related differences in SOCE (store-operated Ca2+ entry) have been minimally investigated. We hypothesized that vascular protection in females, compared with males, reflects decreased Ca2+ mobilization due to diminished activation of Orai 1/STIM 1 (stromal interaction molecule I). In addition, we investigated whether ovariectomy in females affects the activation of the Orai 1/STIM 1 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 Ca2+ influx-induced contractions. Compared with females, aorta from male SHRSP displayed: (i) increased contraction during the Ca2+-loading period; (ii) similar transient contraction during Ca2+ release from the intracellular stores; (iii) increased activation of STIM 1 and Orai1, as shown by the blockade of STIM 1 and Orai1 with neutralizing antibodies, which reversed the sex differences in contraction during the Ca2+-loading period; and (iv) increased expression of STIM I and Orai I. Additionally, we found that aortas from OVX-SHRSP showed increased contraction during the Ca2+-loading period and increased Orai1 expression, but no changes in the SR (sarcoplasmic reticulum)-buffering capacity or STIM I expression. These findings suggest that augmented activation of STIM 1/Orai 1 in aortas from male SHRSP represents a mechanism that contributes to sex-related impaired control of intracellular Ca2+ levels. Furthermore, female sex hormones may negatively modulate the STIM/Orai 1 pathway, contributing to vascular protection observed in female rats. (AU)

• Processo FAPESP: 09/08095-5 - Diferenças sexuais na sinalização STIM1/Orai em artérias de ratos espontaneamente hipertensos
• Beneficiário: Rita de Cassia Aleixo Tostes Passaglia
• Modalidade de apoio: Auxílio à Pesquisa - Regular