title: Effects of tryptophan-containing peptides on angiotensin-converting enzyme activity and vessel tone ex vivo and in vivo.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: Institute of Physiology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, Germany.
authors.forename: Sherif
authors.initials: S
authors.lastname: Khedr
authors.affiliation: Institute of Physiology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Deussen
authors.affiliation: Institute of Physiology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, Germany.
authors.forename: Irakli
authors.initials: I
authors.lastname: Kopaliani
authors.affiliation: Institute of Physiology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Zatschler
authors.affiliation: Institute of Physiology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, Germany. melanie.martin@tu-dresden.de.
authors.forename: Melanie
authors.identifier: http://orcid.org/0000-0003-2524-3124
authors.initials: M
authors.lastname: Martin
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D001011:Aorta / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D002478:Cells, Cultured; D019587:Dietary Supplements; D004151:Dipeptides / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000178:diet therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D055550:Protein Stability; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D014655:Vascular Resistance; D014664:Vasodilation; D014665:Vasodilator Agents / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004151:Dipeptides; D014665:Vasodilator Agents; C509811:tryptophan-leucine; C060736:thymogen
keywords: Angiotensin-converting enzyme; Arterial hypertension; Endothelial cells; Tryptophan-containing peptides; Vessel tone