首页> 外文期刊>The journal of sexual medicine >Endothelin-1 induces contraction of female rat internal pudendal and clitoral arteries through ET(A) receptor and rho-kinase activation.
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Endothelin-1 induces contraction of female rat internal pudendal and clitoral arteries through ET(A) receptor and rho-kinase activation.

机译:内皮素-1通过ET(A)受体和Rho激酶激活诱导雌性大鼠阴部和阴蒂动脉的收缩。

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INTRODUCTION: Endothelin-1 (ET-1), a potent vasoconstrictor peptide, acts mainly through the Gprotein-coupled ET(A) receptor (ET(A)R). Increased vascular ET-1 production and constrictor sensitivity have been observed in various cardiovascular diseases, including hypertension, as well as erectile dysfunction. The internal pudendal artery (IPA) supplies blood to the vagina and clitoris. Inadequate blood flow through the IPA may lead to insufficient vaginal engorgement and clitoral tumescence. AIM: Characterize the effects of ET-1 on the IPA and clitoral artery (CA). METHODS: IPA and CA from female Sprague Dawley rats (225-250 g) were mounted in myograph chambers. Arterial segments were submitted to increasing concentrations of ET-1 (10-10-10-6 M). Segments were incubated with the ET(A)R antagonist, atrasentan (10-8 M) or the Rho-kinase inhibitor, Y-27632 (10-6 M) 30 minutes prior to agonist exposure. All E(max) values are expressed as % KCl-induced maximal contraction. ET(A)R, RhoA, and Rho-kinase expression from IPA was evaluated by Western blot. mRNA of preproET-1, ET(A)R, ET(B)R, RhoA, and Rho-kinase were measured by real time PCR. MAIN OUTCOME MEASURES: ET-1 constrictor sensitivity in IPA and CA, protein expression and messenger RNA levels of ET-1-mediated constriction components. RESULTS: ET-1 concentration-dependently contracted IPA (% Contraction and pD2, respectively: 156 +/- 18, 8.2 +/- 0.1) and CA (163 +/- 12, 8.8 +/- 0.08), while ET(A)R antagonism reduced ET-1-mediated contraction (IPA: 104 +/- 23, 6.4 +/- 0.2; CA: 112 +/- 17, 6.6 +/- 0.08). Pretreatment with Y-27632 significantly shifted ET-1 pD2 in IPA (108 +/- 24, 7.9 +/- 0.1) and CA (147 +/- 58 and 8.0 +/- 0.25). Protein expression of ET(A)R, ET(B)R, RhoA, and Rho-kinase were detected in IPA. IPA and CA contained preproET-1, ET(A)R, ET(B)R, RhoA, and Rho-kinase message. CONCLUSION: We observed that the IPA and CA are sensitive to ET-1, signaling through the ET(A)R and Rho-kinase pathway. These data indicate that ET-1 may play a role in vaginal and clitoral blood flow and may be important in pathologies where ET-1 levels are elevated.
机译:简介:内皮素-1(ET-1)是一种有效的血管收缩肽,主要通过G蛋白偶联的ET(A)受体(ET(A)R)起作用。在包括高血压以及勃起功能障碍在内的各种心血管疾病中,已观察到血管ET-1产生增加和收缩剂敏感性增加。阴部内动脉(IPA)为阴道和阴蒂提供血液。通过IPA的血流不足可能会导致阴道充血不足和阴蒂肿大。目的:表征ET-1对IPA和阴蒂动脉(CA)的作用。方法:将雌性Sprague Dawley大鼠(225-250 g)的IPA和CA置于肌电图仪室中。动脉节段的ET-1(10-10-10-6 M)浓度增加。激动剂暴露前30分钟,将片段与ET(A)R拮抗剂阿曲生坦(10-8 M)或Rho激酶抑制剂Y-27632(10-6 M)孵育。所有E(max)值均表示为%KCl诱导的最大收缩。通过蛋白质印迹评估来自IPA的ET(A)R,RhoA和Rho激酶表达。通过实时PCR测量preproET-1,ET(A)R,ET(B)R,RhoA和Rho激酶的mRNA。主要观察指标:IPA和CA中的ET-1收缩子敏感性,ET-1介导的收缩成分的蛋白表达和信使RNA水平。结果:ET-1浓度依赖性地收缩IPA(收缩百分比和pD2:分别为156 +/- 18、8.2 +/- 0.1)和CA(163 +/- 12、8.8 +/- 0.08),而ET(A R拮抗作用减少了ET-1介导的收缩(IPA:104 +/- 23,6.4 +/- 0.2; CA:112 +/- 17,6.6 +/- 0.08)。使用Y-27632进行预处理可显着改变IPA(108 +/- 24、7.9 +/- 0.1)和CA(147 +/- 58和8.0 +/- 0.25)中的ET-1 pD2。在IPA中检测到ET(A)R,ET(B)R,RhoA和Rho激酶的蛋白表达。 IPA和CA包含preproET-1,ET(A)R,ET(B)R,RhoA和Rho激酶信息。结论:我们观察到IPA和CA对ET-1敏感,通过ET(A)R和Rho激酶途径发出信号。这些数据表明,ET-1可能在阴道和阴蒂的血流中起作用,并且在ET-1水平升高的病理中可能很重要。

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