Sherif Khedr1, Andreas Deussen1, Irakli Kopaliani1, Birgit Zatschler1, Melanie Martin2. 1. Institute of Physiology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, Germany. 2. Institute of Physiology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, Germany. melanie.martin@tu-dresden.de.
Abstract
PURPOSE: Over-activation of the renin-angiotensin axis and worsening of vascular function are critical contributors to the development of hypertension. Therefore, inhibition of angiotensin-converting enzyme (ACE), a key factor of the renin-angiotensin axis, is a first line treatment of hypertension. Besides pharmaceutical ACE inhibitors, some natural peptides have been shown to exert ACE-inhibiting properties with antihypertensive effects and potentially beneficial effects on vascular function. In this study, the ACE-inhibiting potential and effects on vascular function of tryptophan-containing peptides were evaluated. METHODS: The ACE inhibitory action and stability of tryptophan-containing peptides was tested in endothelial cells-a major source of whole body ACE activity. Furthermore, the efficacy of peptides on vascular ACE activity, as well as vessel tone was assessed both ex vivo and in vivo. RESULTS: In human umbilical vein endothelial cells (HUVEC), isoleucine-tryptophan (IW) had the highest ACE inhibitory efficacy, followed by glutamic acid-tryptophan (EW) and tryptophan-leucine (WL). Whereas none of the peptides affected basal vessel tone (rat aorta), angiotensin I-induced vasoconstriction was blocked. IW effectively inhibited aortic ACE activity ex vivo taken from SHRs after 14-weeks of oral treatment with IW. Furthermore, IW treated SHRs showed better endothelium-dependent vessel relaxation compared to placebo. CONCLUSION: This study shows strong ACE-inhibiting effects of IW, EW and WL in HUVECs and aorta. The peptides effectively counteract angiotensin-induced vasoconstriction and preserve endothelium-dependent vessel relaxation. Thus, tryptophan-containing peptides and particularly IW may serve as innovative food additives with the goal of protection from angiotensin II-induced worsening of vascular function.
PURPOSE: Over-activation of the renin-angiotensin axis and worsening of vascular function are critical contributors to the development of hypertension. Therefore, inhibition of angiotensin-converting enzyme (ACE), a key factor of the renin-angiotensin axis, is a first line treatment of hypertension. Besides pharmaceutical ACE inhibitors, some natural peptides have been shown to exert ACE-inhibiting properties with antihypertensive effects and potentially beneficial effects on vascular function. In this study, the ACE-inhibiting potential and effects on vascular function of tryptophan-containing peptides were evaluated. METHODS: The ACE inhibitory action and stability of tryptophan-containing peptides was tested in endothelial cells-a major source of whole body ACE activity. Furthermore, the efficacy of peptides on vascular ACE activity, as well as vessel tone was assessed both ex vivo and in vivo. RESULTS: In human umbilical vein endothelial cells (HUVEC), isoleucine-tryptophan (IW) had the highest ACE inhibitory efficacy, followed by glutamic acid-tryptophan (EW) and tryptophan-leucine (WL). Whereas none of the peptides affected basal vessel tone (rat aorta), angiotensin I-induced vasoconstriction was blocked. IW effectively inhibited aortic ACE activity ex vivo taken from SHRs after 14-weeks of oral treatment with IW. Furthermore, IW treated SHRs showed better endothelium-dependent vessel relaxation compared to placebo. CONCLUSION: This study shows strong ACE-inhibiting effects of IW, EW and WL in HUVECs and aorta. The peptides effectively counteract angiotensin-induced vasoconstriction and preserve endothelium-dependent vessel relaxation. Thus, tryptophan-containing peptides and particularly IW may serve as innovative food additives with the goal of protection from angiotensin II-induced worsening of vascular function.
Authors: Marc A Pfeffer; John J V McMurray; Eric J Velazquez; Jean-Lucien Rouleau; Lars Køber; Aldo P Maggioni; Scott D Solomon; Karl Swedberg; Frans Van de Werf; Harvey White; Jeffrey D Leimberger; Marc Henis; Susan Edwards; Steven Zelenkofske; Mary Ann Sellers; Robert M Califf Journal: N Engl J Med Date: 2003-11-10 Impact factor: 91.245
Authors: Antje Drechsel; Jana Helm; Hermann Ehrlich; Snezana Pantovic; Stefan R Bornstein; Nicole Bechmann Journal: Mar Drugs Date: 2020-05-01 Impact factor: 5.118