인간 자궁동맥에서 내피세포 비의존성 기전을 통한 에스트로겐의 혈관 수축 억제 효과

초록

Objective: This study was performed to investigate whether 1) estrogen induces the change of vascular tone in endothelium-denuded human uterine artery, and 2) endothelium-independent vascular reactivity may be mediated by intracellular calcium ion modulation. Methods: The uterine arteries from 34 premenopausal women were obtained at the time of hysterectomy due to various indications and endothelium was denuded. Vascular reactivity was monitored by using Isometric force transducer and recorded by physiograph. Endothelial integrity was assessed by sequential administration of 1μM norepinephrine(α-adrenergic stimulant) and 10 μM acetylcholine (endothelium -dependent vasorelaxant). Integrity of smooth muscle was measured by administration of 10μM sodium nitroprusside (endothelium - independent vasorelaxant) and 10μM tamsulosin(α-adrenergic blocker). A dose-dependent action of estrogen was measured on denuded uterine arteries, pretreated with norepinephrine and potassium chloride. In media contained denuded uterine arteries pretreated with 70mM potassium chloride and estradiol(3×10-5M), nitric oxide and its inhibitor, N-nitro-L-arginine methyl ester(L-NAME) was administered, respectively, in order to verify the vasodilation effect. Statistical tests were performed at the 5% level of significance using the SPSS PC+ package. Results: Acethylcholine has little effect but sodium nitroprusside & talmsulosin showed marked relaxation, which suggested loss of endothelial function and adequacy of smooth muscle function. The contraction by norephinephrine(1 M) revealed estrogen induced relaxation which was concentration-dependent from 3 10-8M to 3 10-5M in concentration of 17 -estradiol. The contraction by high potassium solution 70mM was also inhibited by estrogen in concentration-dependent manner. This vasorelaxant effect of estrogen on endothelium-denuded uterine artery was not affected by addition of nitric oxide(NO) precursor, L-arginine and nitric oxide synthase(NOS) inhibitor, L-NAME. Conclusion: The results of this study revealed that estrogen has vasorelaxant effect on endothelium endothelium-denuded uterine artery by calcium antagonistic property through direct inhibitory effect on receptor- and voltage dependent calcium ion channels of smooth muscles. This vasorelaxant effect of estrogen on endothelium-denuded uterine artery was NO independent.

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