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首页> 外文期刊>The journal of sexual medicine >Enhanced Electrical Field Stimulated Nitrergic and Purinergic Vasoreactivity in Distal vs Proximal Internal Pudendal Arteries
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Enhanced Electrical Field Stimulated Nitrergic and Purinergic Vasoreactivity in Distal vs Proximal Internal Pudendal Arteries

机译：增强的电场刺激了邻近内部疏水动脉远端Vs的硝态能和嘌呤能血管反应性

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Abstract Background The internal pudendal arteries (IPAs) supply blood to the penis and are highly susceptible to vascular remodeling in rodent models of diabetes, hypertension, aging, and chronic kidney disease, thus contributing to erectile dysfunction. Interestingly, vascular remodeling primarily occurs in the distal and not in the proximal IPA, suggesting distinct local physiologic signaling differences within the IPA. Aim To examine the role of purinergic signaling and neurotransmitter release by electrical field stimulation (EFS) in the regulation of proximal and distal IPA vascular tone. Methods Proximal and distal IPAs were mounted in wire myographs and vascular responses to phenylephrine, acetylcholine, and 2-(N,N-diethylamino)-diazenolate-2-oxide, diethyl-ammonium salt (DEA NONOate) were measured. EFS-mediated contraction and non-adrenergic non-cholinergic (NANC) relaxation were evaluated in the absence and presence of a nitric oxide synthase antagonist. Purinergic agonist and NANC relaxation responses were assessed in the presence and absence of P2X1 and P2Y1 antagonists. Protein expression of P2X1 and P2Y1 receptors was measured by western blot. Main Outcome Measures Proximal and distal IPA contraction and relaxation were measured during increasing agonist administration and EFS in the presence and absence of antagonists. Results Proximal and distal IPA concentration response curves to phenylephrine, acetylcholine, and DEA NONOate did no differ. Interestingly, distal IPA exhibited greater EFS-mediated contraction and NANC relaxation compared with proximal IPA. Nitric oxide synthase inhibition completely inhibited distal IPA NANC relaxation but did not affect proximal IPA relaxation. P2X1 or P2Y1 receptor antagonism during NANC?relaxation increased distal IPA relaxation but decreased proximal IPA relaxation. Combined P2X1 and P2Y1 receptor antagonism had no effect on proximal IPA relaxation but significantly increased distal IPA NANC relaxation. Clinical Translation Understanding neurovascular regulation of IPA vascular tone through nitrergic and purinergic mechanisms could yield new therapeutic targets to improve IPA blood flow and treat vasculogenic erectile dysfunction. Strengths and Limitations This study is the first to illustrate the differences in mechanisms responsible for regulating vascular tone in the proximal and distal IPAs. All presented findings are currently limited to ex?vivo vascular function. Conclusion The regulation of vascular tone differs regionally in the IPA. The distal IPA is controlled through neurotransmitter-mediated NO-dependent mechanisms and increased sensitivity to purinergic P2X1 and P2Y1 receptor inhibition. Odom MR, Pak ES, Brown DA, Hannan JL. Enhanced Electrical Field Stimulated Nitrergic and Purinergic Vasoreactivity in Distal vs Proximal Internal Pudendal Arteries. J Sex Med 2017;14:1285–1296.
机译：摘要背景内部pudendal动脉（IPA）为阴茎供应血液，对糖尿病，高血压，老化和慢性肾病的啮齿动物模型中的血管改造高度敏感，因此有助于勃起功能障碍。有趣的是，血管重塑主要发生在远端而不是在近端IPA中，表明IPA内的不同局部生理信号传导差异。目的在于近端和远端IPA血管间调的调节中，通过电场刺激（EFS）来检查嘌呤能信号传导和神经递质释放的作用。方法将近端和远端IPA安装在线映号中，对苯甲酸肾上腺素，乙酰胆碱和2-（N，N-二乙基氨基） - 氧化乙酯-2-氧化物，测定乙酰铵盐（DEA非盐）的血管反应。在没有氧化氮合酶拮抗剂的情况下评估EFS介导的收缩和非肾上腺素能非胆碱能（NANC）弛豫。在P2X1和P2Y1拮抗剂的存在和不存在下评估嘌呤能激动剂和NANC弛豫响应。通过Western印迹测量P2X1和P2Y1受体的蛋白质表达。在增加激动剂给药和EF在存在和不存在拮抗剂时测量主要结果测量近端和远端IPA收缩和放松。结果近端和远端IPA浓度响应曲线向苯妥，乙酰胆碱和DEA不酸酯没有差异。有趣的是，与近期IPA相比，远端IPA表现出更大的EFS介导的收缩和NANC放松。一氧化氮合成酶抑制完全抑制了远端IPA NANC弛豫，但不影响近端IPA松弛。在NANC期间P2X1或P2Y1受体对拮抗作用增加了远端IPA松弛，但近端IPA松弛下降。组合的P2X1和P2Y1受体拮抗作用对近端IPA松弛没有影响，但显着增加了远端IPA NANC SOLLATION。临床翻译了解通过氮和嘌呤能机制的神经血管调节IPA血管间调可以产生新的治疗目标，以改善IPA血液流动和治疗血管原勃起功能障碍。该研究的优势和局限性是第一个说明负责调节近端和远端IPAS中血管间调的机制差异的差异。所有呈现的调查结果目前仅限于EX？体内血管功能。结论IPA地区的血管间距的调节不同。远端IPA通过神经递质介导的无依赖性机制来控制，并增加对嘌呤能P2X1和P2Y1受体抑制的敏感性。 Odom Mr，Pak Es，Brown Da，Hannan JL。增强的电场刺激了远端Vs近端硫态动脉中的氮气性和嘌呤能激光率。 J SEX MED 2017; 14：1285-1296。

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