{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T15:56:44Z","timestamp":1779897404192,"version":"3.53.1"},"reference-count":27,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,9,22]],"date-time":"2015-09-22T00:00:00Z","timestamp":1442880000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["0315473A"],"award-info":[{"award-number":["0315473A"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Angiotensin\u2010converting 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 <jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content>\u2010inhibiting peptides derived from food proteins in spontaneously hypertensive rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>Isoleucine\u2013tryptophan (<jats:italic>in\u00a0vitro <\/jats:italic><jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content><jats:sub>50<\/jats:sub> for <jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content>\u00a0= 0.7 <jats:italic>\u03bc<\/jats:italic><jats:sc>m<\/jats:sc>), a whey protein hydrolysate containing an augmented fraction of isoleucine\u2013tryptophan, or captopril was given to spontaneously hypertensive rats (<jats:italic>n<\/jats:italic>\u00a0=\u00a060) over 14\u00a0weeks. Two further groups, receiving either no supplement (Placebo) or intact whey protein, served as controls. Systolic blood pressure age\u2010dependently increased in the Placebo group, whereas the blood pressure rise was effectively blunted by isoleucine\u2013tryptophan, whey protein hydrolysate and captopril (\u221242\u00a0\u00b1\u00a03, \u221238\u00a0\u00b1\u00a05, \u221255\u00a0\u00b1 4\u00a0mm Hg vs. Placebo). At study end, myocardial mass was lower in isoleucine\u2013tryptophan and captopril groups but only partially in the hydrolysate group. Coronary flow reserve (1\u00a0<jats:italic>\u03bc<\/jats:italic><jats:sc>m<\/jats:sc> adenosine) was improved in isoleucine\u2013tryptophan and captopril groups. Plasma <jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content> activity was significantly decreased in isoleucine\u2013tryptophan, hydrolysate and captopril groups, but in aortic tissue only after isoleucine\u2013tryptophan or captopril treatment. This was associated with lowered expression and activity of matrix metalloproteinase\u20102. Following isoleucine\u2013tryptophan and captopril treatments, gene expression of renin was significantly increased indicating an active feedback within renin\u2013angiotensin system.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Whey protein hydrolysate and isoleucine\u2013tryptophan powerfully inhibit plasma <jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content> resulting in antihypertensive effects. Moreover, isoleucine\u2013tryptophan blunts tissue <jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content> activity, reduces matrix metalloproteinase\u20102 activity and improves coronary flow reserve. Thus, whey protein hydrolysate and particularly isoleucine\u2013tryptophan may serve as innovative food additives with the goal of attenuating hypertension.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.12578","type":"journal-article","created":{"date-parts":[[2015,8,22]],"date-time":"2015-08-22T15:01:11Z","timestamp":1440255671000},"page":"167-176","source":"Crossref","is-referenced-by-count":38,"title":["Antihypertensive and cardioprotective effects of the dipeptide isoleucine\u2013tryptophan and whey protein hydrolysate"],"prefix":"10.1111","volume":"215","author":[{"given":"M.","family":"Martin","sequence":"first","affiliation":[{"name":"Institute of Physiology Medical Faculty TU Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Kopaliani","sequence":"additional","affiliation":[{"name":"Institute of Physiology Medical Faculty TU Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Jannasch","sequence":"additional","affiliation":[{"name":"Cardiac Surgery Heart Center Dresden at TU Dresden TU Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Mund","sequence":"additional","affiliation":[{"name":"Institute of Physiology Medical Faculty TU Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Todorov","sequence":"additional","affiliation":[{"name":"Division of Nephrology Department of Internal Medicine III University Hospital Carl Gustav Carus at TU Dresden TU Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Henle","sequence":"additional","affiliation":[{"name":"Institute of Food Chemistry Faculty of Science TU Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Deussen","sequence":"additional","affiliation":[{"name":"Institute of Physiology Medical Faculty TU Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,9,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.010909.105610"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-008-0336-0"},{"key":"e_1_2_8_4_1","first-page":"85","volume-title":"The World Health Report 2003 \u2010 Shaping the Future. 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