Differential regulation of K+ and Ca2+ channel gene expression by chronic treatment with estrogen and tamoxifen in rat aorta.
The beneficial effect of estrogen on the vascular system is partly associated with its ability to reduce vascular contractility. Estrogen acutely activates large-conductance Ca(2+)-activated K(+) channel (BK(Ca)) and inhibits L-type voltage-gated Ca(2+) channel (VGCC) in vascular smooth muscle cells. However, a long-term influence of estrogen, estrogen deficiency, or selective estrogen receptor modulators on gene expression of these ion channels is unclear. This study was therefore aimed to determine the relative mRNA expression levels of alpha- and beta-subunits of BK(Ca), K(V)1.5 subtype of delayed rectifier K(+) channel (K(V)), and alpha(1C) subunit of L-type VGCC in endothelium-denuded aortas from female rats by a semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis. Rats were divided into four experimental groups: (i) sham-operated control, (ii) ovariectomized, (iii) ovariectomized with 17 beta-estradiol treatment and (iv) ovariectomized with tamoxifen treatment. The results showed that ovariectomy decreased the mRNA expression of K(V)1.5 while it increased the mRNA expression of alpha(1C) subunit of L-type VGCC. Ovariectomy-induced modulation of gene expression of these ion channels was completely prevented in ovariectomized rats receiving chronic treatment with estrogen or tamoxifen. In contrast, the expression levels of genes encoding both alpha- and beta-subunits of BK(Ca) remained the same in the four animal groups. The present study has provided the first line of evidence suggesting the long-term beneficial effects of estrogen and tamoxifen therapy on vascular ion channel expressions, which may be an important mechanism by which the favorable modulation of vessel tone by estrogen or selective estrogen receptor modulators is mediated.
Tsang
Suk Ying
SY
Department of Physiology, Faculty of Medicine, Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.
Yao
Xiaoqiang
X
Wong
Chi Ming
CM
Chan
Franky Leung
FL
Chen
Zhen-Yu
ZY
Huang
Yu
Y
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism; D015220:Calcium Channels / Q000096:biosynthesis* / Q000235:genetics; D004967:Estrogens / Q000008:administration & dosage*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D010052:Ovariectomy; D015221:Potassium Channels / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013629:Tamoxifen / Q000008:administration & dosage*
D015220:Calcium Channels; D004967:Estrogens; D015221:Potassium Channels; D012333:RNA, Messenger; D013629:Tamoxifen