在健康志愿者中进行的为期4周的安慰剂对照、双盲、交叉试验中,抑制ACE1的乳三肽可急剧提高血浆缓激肽浓度

J. Nussberger, A. Dubach, A. Turpeinen, H. Vapaatalo
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引用次数: 2

摘要

这项由12名血压正常的健康志愿者组成的安慰剂对照、双盲交叉干预试验,测试了含有5毫克或50毫克ace1抑制乳三肽(异亮氨酸-脯氨酸-脯氨酸,Ile-Pro-Pro和缬氨酸-脯氨酸-脯氨酸,缬氨酸-pro -pro)和安慰剂乳饮料(味道相似)对血浆缓激肽水平的影响。受试者以随机顺序、双盲、为期四周的试验方式食用三种测试产品中的一种。在第一天(第1天)和最后一天(第29天),即使用其中一种产品治疗四周后,测定相同单次剂量的急性效应。其他肾素-血管紧张素-醛固酮系统(RAAS)的标志物在同一天从血浆中测量了四次,同时我们也评估了内皮功能生物标志物的日间尿排泄。急性或长期服用ACE-1抑制肽饮料均不能显著降低血压正常者的血压。最重要的发现是在第一天急性给药后血浆缓激肽浓度呈剂量依赖性和线性增加;在第29天也几乎具有统计学意义(p 0.06)。急性或长期治疗后,RAAS或内皮功能的其他指标与安慰剂组没有差异。我们的研究结果表明,即使是较弱的ACE-1抑制剂,如乳三肽Ile-Pro-Pro和Val-Pro-Pro,也能够减少缓激肽的分解,从而增加血浆缓激肽水平。这可能部分解释了我们之前在轻度高血压患者中发现的乳三肽的降血压和血管扩张作用。
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Lactotripeptides Inhibiting ACE1 Elevate the Plasma Bradykinin Concentration Acutely in a Placebo-Controlled, Double-Blind, Cross-Over, 4-Week Trial in Healthy Volunteers
This placebo-controlled, double-blind, cross-over intervention with twelve normotensive healthy volunteers tested the effects of milk products containing either 5 or 50 mg of ACE1-inhibitory lactotripeptides (isolecine-proline-proline, Ile-Pro-Pro, and valine-proline-proline, Val-Pro-Pro) and placebo milk drink (with similar taste) on plasma bradykinin levels. The subjects consumed one of the three test products in a random order, double-blinded, and four-week trial. On the first day (day 1) and on the last day (day 29) i.e. after four weeks’ treatment with one of the products, the acute effect with the same single dose was assayed. Other markers of the renin-angiotensin-aldosterone system (RAAS) were measured from plasma four times on the same days when we also assessed daytime urinary excretion of biomarkers of endothelial function. Neither acute nor prolonged administration of the ACE-1 inhibiting peptide drinks significantly lowered blood pressure of the normotensive subjects. The most important finding was the dose-dependent, and linear increase in plasma bradykinin concentrations after acute dosing on the first day; it was nearly statistically significant also on the day 29 (p 0.06). Other indicators of RAAS or endothelial function did not differ from those of placebo after the acute or prolonged treatments. Our results suggest that even weak inhibitors of ACE-1, such as the lactotripeptides Ile-Pro-Pro and Val-Pro-Pro, are able to diminish the breakdown of bradykinin and therefore increase plasma bradykinin levels. This may partly explain the blood pressure lowering and vasodilatory effects of lactotripeptides, shown by us earlier in mildly hypertensive subjects.
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