Constrictor prostanoid-potentiated vascular contraction: regulation of endothelial and vascular smooth muscle mechanism by estrogen
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The objectives of this research were to elucidate the involvement of constrictor prostanoids in the vascular reactivity to vasopressin (VP) and the role of estrogen in the regulation of the constrictor prostanoid mechanism in the female rat. Aortas obtained from male, intact (InT)-, ovariectomized (OvX)- and OvX + estrogen-replaced (OvX+Est)-female rats were studied. Contractile responses to VP were examined in the presence of nonselective and selective cyclooxygenase (COX) inhibitors. Basal and VP-stimulated release of thromboxane A2 (TxA2) and prostacyclin (PGI2) from the aortic wall were measured. Concentration-response curves to exogenous TxA2 were also obtained. To elucidate the regulatory effects of estrogen on the constrictor prostanoid pathway, the expression of COX-1, COX-2, thromboxane synthase (TxS) and thromboxane receptor (TP) mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR). Further, immunohistochemistry was employed to determine COX-1, COX-2 and TxS protein expression in aortic endothelium and vascular smooth muscle. The major findings of this research are that: 1) The contractile responses of the female rat aorta to VP were enhanced by COX-2-mediated production of constrictor prostanoids (PGH2/TxA2), and this mechanism is potentiated by estrogen; 2) Vascular reactivity to exogenous TxA2 was higher in the female than in the male rat aorta, and OvX attenuated and estrogen replacement therapy restored vascular reactivity to TxA2 in the female aorta; 3) VP-stimulated release of endogenous TxA2 and PGI2 were higher in the female than in the male rat aorta, and OvX attenuated and estrogen replacement therapy restored VP-stimulated release of these endogenous prostanoids by the female aorta; and 4) The expression of COX-2 and TxS mRNA and protein, and the expression of TP mRNA were higher in InT-female than in male, and were reduced by OvX and restored by estrogen replacement therapy. In conclusion, estrogen potentiated contractile responses of the female rat aorta to VP by upregulating the expression of COX-2, TxS and TP; thereby enhancing VP-induced release of TxA2, as well as the vascular reactivity to endogenous TxA2.
Li, Min (2005). Constrictor prostanoid-potentiated vascular contraction: regulation of endothelial and vascular smooth muscle mechanism by estrogen. Doctoral dissertation, Texas A&M University. Texas A&M University. Available electronically from