인간 자궁동맥에서 에스트로겐의 혈관 평활근 세포막 칼슘과 포타슘 이온 통로를 통한 혈관 이완 효과

초록

Cardiovascular disease remains a major cause of mortality of postmenopausal women in Korea. Many lines of recent evidence from clinical and experimental studies strongly support that estrogen is not only a reproductive hormone but also a powerful cardiovascular active substance. Postmenopausal estrogen replacement therapy reduces cardiovascular risk by approximately 50% but cardioprotective mechanisms of estrogen have not been fully elucidated yet, The present study was carried out to evaluate the possible direct vasorelaxation effect of estrogen and the role of smooth muscle cell membrane calcium and potassium ion channels in vasorelaxation by use of human uterine arteries obtained by hysterectomy. Vascular reactivity was assessed by high potassium depolarization medium(70mMol) and tetraethylammonium(10mM) for the stimulation of voltage-dependent calcium ion channel and blockade of potassium ion channel respectively. Following results were obtained. 1. The contraction curve in high potassium-depolarization medium showed estrogen concentration-dependent relaxation in human uterine artery preparations preincubated with 17B-estradiol of 4 kinds of concentrations from 3*10-8M to 3*10-5M for shott-term duration(30 minutes), 2. Blockade of activity of potassium ion channel with tetraethylammonium(TEA) inhibited estrogen-induced relaxation of human uterine artery preparations contracted by high extracellular potassium. 3. N-nitro-L-arginine methyl ester(L-NAME), an inhibitor of nitric oxide(NO) synthesis from L-arginine did not affect the relaxant effect of 17B-estradiol on contraction of uterine artery prepatarions induced by high potassium medium, which suggested that the activation of potassium channel by estrogen is not NO-dependent. These results showed that estrogen may have concentration-dependent inhibitory effect on vasoconstriction responses and a calcium antagonistic property through direct inhibitory effect on voltage-dependent calcium ion channels and indirect action via stimulation on potassium ion channels of vascular smooh muscle cell membrane. This mechanism may partly explain the cardiovascular protective effects of estrogen.

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