Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCB025

Poster Communications

The ACE-inhibitory effects of Isoleucine-Tryptophan after oral intake in man.

M. Martin1, D. Hagemann2, T. Henle2, A. Deussen1

1. Institute of Physiology, TU Dresden, Dresden, Germany. 2. Institute of Food Chemistry, TU Dresden, Dresden, Germany.


Angiotensin-Converting Enzyme (ACE)-inhibitors are treatment of choice in hypertensive patients. Some natural peptides from food proteins have structural similarities with pharmaceutical ACE-inhibitors and show ACE-inhibiting action. Because hypertension is a public health problem worldwide, such peptides may be of interest for early treatment or disease delay for mild hypertensives. We revealed the ACE-inhibition and antihypertensive effect of the natural dipeptide isoleucine-tryptophan (IW) and its effect on cardiac remodelling and coronary flow reserve in spontaneously hypertensive rats. However, especially with using IW for preventive purposes, the effectiveness has to be proven in man. Thus, aims of this project were to determine the ACE-inhibiting effect and bioavailability of IW after 1) oral intake of whey hydrolysate with high content of IW (MPH) in man, and 2) combined intake of MPH with food ingredients and 3) effects on blood pressure after intake of MPH. Normotensive volunteers received MPH in different doses (n=10), intact whey protein (n=2) or water (n=8). MPH was applied alone or combined with intake of oats, protein, carbohydrates or fat; n=8). Blood samples were taken at fixed time points for analysis of ACE activity (in vitro, using the substrate Hip-His-Leu) and assessment of IW concentration in plasma by LC-MS/MS method. Blood pressure was assessed in a randomized double-blinded manner. Values are mean±SD, compared by ANOVA. Intake of 10g MPH (equivalent to 50mg IW) induced a decrease in plasma ACE activity to 82±4% (p<0.05) of baseline ACE activity and an increase in plasma IW concentrations (max. 20±5nM, p<0.05). The maximum of ACE inhibition coincided with the peak IW concentration. 50g MPH increased plasma IW concentrations to 99±58nM (p<0.05). In parallel, ACE activity was decreased to 75±7% (p<0.05). Intake of non-hydrolysed whey protein increased IW concentration only to 4±1nM and decreased ACE activity to 90±3%. No changes in IW plasma concentration and ACE activities were observed following water application. Combined intake with food ingredients extended the IW rise of plasma concentration and ACE inhibition. With carbohydrates the ACE inhibition was diminished. No change in systolic and diastolic blood pressure was found after intake of 10g MPH or water. Thus, in healthy volunteers oral intake of IW alone or with other food ingredients results in an increase of IW plasma concentration and ACE inhibition in normotensives without unwanted hypotensive effects. However, the ACE inhibition cannot be explained by the peptide concentration achieved in plasma considering the in vitro IC50 (0.7µM). Further studies are mandatory to clarify the underlying cause-effect relationship for peptide ACE inhibitors in order to further developing innovative food additives with preventive effects on ACE activation and related cardiovascular diseases.

Where applicable, experiments conform with Society ethical requirements