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上皮钠离子通道阻断和新的β-ENaC 多态性在正常血压和高血压的尼日利亚成年人中。

Epithelial sodium channel blockade and new β-ENaC polymorphisms among normotensive and hypertensive adult Nigerians.

机构信息

Department of Physiology, Lagos State University College of Medicine, Lagos, Nigeria.

Department of Physiology, College of Medicine University of Lagos, Lagos, Nigeria.

出版信息

Clin Exp Hypertens. 2019;41(2):144-151. doi: 10.1080/10641963.2018.1451538. Epub 2018 Mar 26.

Abstract

We sought to determine the effect of amiloride on blood pressure (BP) and the presence of polymorphisms of the β-subunit of the epithelial sodium channel (ENaC) among normotensive (NT) and hypertensive (HT) Nigerians. Healthy volunteers-47 NT and 53 age-matched HT were recruited after giving informed consent. Subjects were salt-loaded with 200 mmol of NaCl daily for 5 days. Following a week washout period, salt-loading was repeated in addition to the administration of 5 mg amiloride daily for five days. Blood pressure, plasma and urine electrolytes were measured at baseline, after salt-loading and after salt-loading plus amiloride. PCR amplicons were sequenced for β-ENaC polymorphisms. Salt-loading led to a significant increase (p < 0.05) in SBP among NT and HT and in DBP (p < 0.001) only among HT. Amiloride reduced SBP and DBP to below baseline levels in NT (p < 0.05) and HT (p < 0.001) subjects. Five of the subjects had the β-T594M polymorphism, HT 3/53; NT 2/47 (p = 0.75). Four previously unreported β-ENaC mutations were recorded: E632V and E636V, respectively, among two HT subjects, D638Y in another HT and L628Q in one NT subject. We showed the presence of β-ENaC polymorphisms among our populace and the possible usefulness of amiloride as a single antihypertensive among Nigerians.

摘要

我们旨在探讨阿米洛利对血压(BP)的影响,以及β-上皮钠通道(ENaC)亚基在尼日利亚正常血压(NT)和高血压(HT)人群中的多态性。在知情同意后,招募了 47 名 NT 和 53 名年龄匹配的 HT 健康志愿者。受试者每天接受 200mmol NaCl 盐负荷 5 天。在一周洗脱期后,在进行盐负荷的同时,每天给予 5mg 阿米洛利,持续 5 天。在基线、盐负荷后和盐负荷加阿米洛利后测量血压、血浆和尿液电解质。对β-ENaC 多态性进行 PCR 扩增子测序。盐负荷导致 NT 和 HT 组 SBP 显著增加(p<0.05),仅 HT 组 DBP 显著增加(p<0.001)。阿米洛利使 NT(p<0.05)和 HT(p<0.001)受试者的 SBP 和 DBP 降至低于基线水平。5 名受试者存在β-T594M 多态性,HT 组 3/53,NT 组 2/47(p=0.75)。记录到 4 种以前未报道的β-ENaC 突变:分别在 2 名 HT 受试者和 1 名 NT 受试者中发现 E632V 和 E636V,另一名 HT 受试者中发现 D638Y,1 名 NT 受试者中发现 L628Q。我们在人群中发现了β-ENaC 多态性,并且阿米洛利可能对尼日利亚人具有单一抗高血压作用。

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