J. Nussberger, A. Dubach, A. Turpeinen, H. Vapaatalo
{"title":"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","authors":"J. Nussberger, A. Dubach, A. Turpeinen, H. Vapaatalo","doi":"10.4236/PP.2018.97017","DOIUrl":null,"url":null,"abstract":"This placebo-controlled, double-blind, cross-over \nintervention with twelve normotensive healthy volunteers tested the effects of \nmilk products containing either 5 or 50 mg \nof ACE1-inhibitory lactotripeptides (isolecine-proline-proline, Ile-Pro-Pro, and valine-proline-proline, \nVal-Pro-Pro) and placebo milk drink (with similar taste) on plasma bradykinin \nlevels. The subjects consumed one of the three test products in a random order, \ndouble-blinded, and four-week trial. On the \nfirst day (day 1) and on the last day (day 29) i.e. after four weeks’ treatment with one of \nthe products, the acute effect with the same single dose was assayed. Other \nmarkers of the renin-angiotensin-aldosterone system (RAAS) were measured from \nplasma four times on the same days when we also assessed daytime urinary \nexcretion of biomarkers of endothelial function. Neither acute nor prolonged \nadministration of the ACE-1 inhibiting peptide drinks significantly lowered \nblood pressure of the normotensive subjects. The most important finding was the \ndose-dependent, and linear increase in plasma \nbradykinin concentrations after acute dosing on the first day; it was nearly \nstatistically significant also on the day 29 (p 0.06). Other indicators of RAAS or endothelial function did not differ \nfrom those of placebo after the acute or prolonged treatments. Our results \nsuggest that even weak inhibitors of ACE-1, such as the lactotripeptides \nIle-Pro-Pro and Val-Pro-Pro, are able to diminish the breakdown of bradykinin \nand therefore increase plasma bradykinin levels. This may partly explain the \nblood pressure lowering and vasodilatory effects of lactotripeptides, shown by \nus earlier in mildly hypertensive subjects.","PeriodicalId":19875,"journal":{"name":"Pharmacology & Pharmacy","volume":"39 1","pages":"229-241"},"PeriodicalIF":0.0000,"publicationDate":"2018-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"2","resultStr":"{\"title\":\"Lactotripeptides Inhibiting ACE1 Elevate the Plasma Bradykinin Concentration Acutely in a Placebo-Controlled, Double-Blind, Cross-Over, 4-Week Trial in Healthy Volunteers\",\"authors\":\"J. Nussberger, A. Dubach, A. Turpeinen, H. Vapaatalo\",\"doi\":\"10.4236/PP.2018.97017\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"This placebo-controlled, double-blind, cross-over \\nintervention with twelve normotensive healthy volunteers tested the effects of \\nmilk products containing either 5 or 50 mg \\nof ACE1-inhibitory lactotripeptides (isolecine-proline-proline, Ile-Pro-Pro, and valine-proline-proline, \\nVal-Pro-Pro) and placebo milk drink (with similar taste) on plasma bradykinin \\nlevels. The subjects consumed one of the three test products in a random order, \\ndouble-blinded, and four-week trial. On the \\nfirst day (day 1) and on the last day (day 29) i.e. after four weeks’ treatment with one of \\nthe products, the acute effect with the same single dose was assayed. Other \\nmarkers of the renin-angiotensin-aldosterone system (RAAS) were measured from \\nplasma four times on the same days when we also assessed daytime urinary \\nexcretion of biomarkers of endothelial function. Neither acute nor prolonged \\nadministration of the ACE-1 inhibiting peptide drinks significantly lowered \\nblood pressure of the normotensive subjects. The most important finding was the \\ndose-dependent, and linear increase in plasma \\nbradykinin concentrations after acute dosing on the first day; it was nearly \\nstatistically significant also on the day 29 (p 0.06). Other indicators of RAAS or endothelial function did not differ \\nfrom those of placebo after the acute or prolonged treatments. Our results \\nsuggest that even weak inhibitors of ACE-1, such as the lactotripeptides \\nIle-Pro-Pro and Val-Pro-Pro, are able to diminish the breakdown of bradykinin \\nand therefore increase plasma bradykinin levels. This may partly explain the \\nblood pressure lowering and vasodilatory effects of lactotripeptides, shown by \\nus earlier in mildly hypertensive subjects.\",\"PeriodicalId\":19875,\"journal\":{\"name\":\"Pharmacology & Pharmacy\",\"volume\":\"39 1\",\"pages\":\"229-241\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2018-07-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmacology & Pharmacy\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.4236/PP.2018.97017\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacology & Pharmacy","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.4236/PP.2018.97017","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
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.