title: Antihypertensive and cardioprotective effects of the dipeptide isoleucine-tryptophan and whey protein hydrolysate.
abstract: OBJECTIVE
  Angiotensin-converting enzyme inhibitors are treatment of choice in hypertensive patients. Clinically used inhibitors exhibit a structural similarity to naturally occurring peptides. This study evaluated antihypertensive and cardioprotective effects of ACE-inhibiting peptides derived from food proteins in spontaneously hypertensive rats.
  
  
  RESULTS
  Isoleucine-tryptophan (in vitro IC50 for ACE = 0.7 μm), a whey protein hydrolysate containing an augmented fraction of isoleucine-tryptophan, or captopril was given to spontaneously hypertensive rats (n = 60) over 14 weeks. Two further groups, receiving either no supplement (Placebo) or intact whey protein, served as controls. Systolic blood pressure age-dependently increased in the Placebo group, whereas the blood pressure rise was effectively blunted by isoleucine-tryptophan, whey protein hydrolysate and captopril (-42 ± 3, -38 ± 5, -55 ± 4 mm Hg vs. Placebo). At study end, myocardial mass was lower in isoleucine-tryptophan and captopril groups but only partially in the hydrolysate group. Coronary flow reserve (1 μm adenosine) was improved in isoleucine-tryptophan and captopril groups. Plasma ACE activity was significantly decreased in isoleucine-tryptophan, hydrolysate and captopril groups, but in aortic tissue only after isoleucine-tryptophan or captopril treatment. This was associated with lowered expression and activity of matrix metalloproteinase-2. Following isoleucine-tryptophan and captopril treatments, gene expression of renin was significantly increased indicating an active feedback within renin-angiotensin system.
  
  
  CONCLUSIONS
  Whey protein hydrolysate and isoleucine-tryptophan powerfully inhibit plasma ACE resulting in antihypertensive effects. Moreover, isoleucine-tryptophan blunts tissue ACE activity, reduces matrix metalloproteinase-2 activity and improves coronary flow reserve. Thus, whey protein hydrolysate and particularly isoleucine-tryptophan may serve as innovative food additives with the goal of attenuating hypertension.
authors: Institute of Physiology, Medical Faculty, TU Dresden, Germany.
authors: M
authors: M
authors: Martin
authors: Institute of Physiology, Medical Faculty, TU Dresden, Germany.
authors: I
authors: I
authors: Kopaliani
authors: Cardiac Surgery, Heart Center Dresden at TU Dresden, TU Dresden, Germany.
authors: A
authors: A
authors: Jannasch
authors: Institute of Physiology, Medical Faculty, TU Dresden, Germany.
authors: C
authors: C
authors: Mund
authors: Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus at TU Dresden, TU Dresden, Germany.
authors: V
authors: V
authors: Todorov
authors: Institute of Food Chemistry, Faculty of Science, TU Dresden, Germany.
authors: T
authors: T
authors: Henle
authors: Institute of Physiology, Medical Faculty, TU Dresden, Germany.
authors: A
authors: A
authors: Deussen
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004151:Dipeptides / Q000494:pharmacology*; D004195:Disease Models, Animal; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D007532:Isoleucine / Q000494:pharmacology; D008297:Male; D011492:Protein Hydrolysates / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D012084:Renin-Angiotensin System / Q000187:drug effects; D014364:Tryptophan / Q000494:pharmacology; D000067796:Whey / Q000737:chemistry*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002316:Cardiotonic Agents; D004151:Dipeptides; D011492:Protein Hydrolysates; D007532:Isoleucine; D014364:Tryptophan; D002216:Captopril
keywords: angiotensin-converting enzyme; arterial hypertension; cardiac hypertrophy; matrix metalloproteinases; whey proteins