Antihypertensive Peptides from Milk Proteins
Abstract
:1. Introduction
2. Milk and Blood Pressure
2.1. Minerals
2.2. Protein
3. Generation of Antihypertensive Peptides from Milk Protein
3.1. Gastrointestinal Digestion
3.2. Fermentation of Milk with Proteolytic Starter Cultures
3.3. Enzymatic Hydrolysis
4. Occurrence of Antihypertensive Peptides in Dairy Products
5. Animal studies
5.1. Casein-Derived Peptides
5.2. Whey-Derived Peptides
6. Clinical Studies
6.1. Casein-Derived Peptides
6.2. Whey-Derived Peptides
7. Bioavailability
8. Mechanisms
9. Biochemical Aspects
10. Safety Aspects
11. Milk Products as Functional Foods
12. Conclusions
Acknowledgements
References
- Kearney, P.M.; Whelton, M.; Reynolds, K.; Muntner, P.; Whelton, P.K.; He, J. Global burden of hypertension. Lancet 2005, 365, 217–223. [Google Scholar] [PubMed]
- Collins, R.; MacMahon, S. Blood pressure, antihypertensive drug treatment and the risks of stroke and coronary heart disease. Br. Med. Bull. 1994, 50, 272–298. [Google Scholar] [PubMed]
- Krousel-Wood, M.A.; Muntner, P.; He, J.; Whelton, P.K. Primary prevention of essential hypertension. Med. Clin. North. Am. 2004, 88, 223–238. [Google Scholar] [CrossRef] [PubMed]
- Chobanian, A.V.; Bakris, G.L.; Black, H.R.; Cushman, W.C.; Green, L.A.; Izzo, J.L.; Jones, D.W.; Materson, B.J.; Oparil, S. National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003, 289, 2560–2572. [Google Scholar] [CrossRef] [PubMed]
- USDA National Nutrient database for Standard Reference. Available online: http://www.nal.usda.gov/fnic/ foodcomp/search/ accessed November 2009.
- Mansbridge, R.L.; Blake, J.S. Nutritional factors affecting the fatty acid composition of bovine milk. Br. J. Nutr. 1997, 78, 37–47. [Google Scholar] [CrossRef]
- McCarron, D.A.; Morris, C.D.; Henry, H.J.; Stanton, J.L. Blood pressure and nutrient intake in the United States. Science 1984, 224, 1392–1398. [Google Scholar] [PubMed]
- Alonso, A.; Steffen, L.M.; Folsom, A.R. Dairy intake and changes in blood pressure over 9 years: The ARIC study. Eur. J. Clin. Nutr. 2009, 63, 1272–1275. [Google Scholar] [CrossRef] [PubMed]
- Wang, L. Dietary intake of dairy products, calcium, and vitamin D and the risk of hypertension in middle-aged and older women. Hypertension 2008, 51, 1073–1079. [Google Scholar] [CrossRef] [PubMed]
- Toledo, E.; Delgado-Rodríguez, M.; Estruch, R.; Salas-Salvadó, J.; Corella, D.; Gomez-Gracia, E.; Fiol, M.; Lamuela-Raventós, R.M.; Schröder, H.; Arós, F.; Ros, E.; Ruíz-Gutiérrez, V.; Lapetra, J.; Conde-Herrera, M.; Sáez, G.; Vinyoles, E.; Martínez-González, MA. Low-fat dairy products and blood pressure: Follow-up of 2290 older persons at high cardiovascular risk participating the PREDIMED study. Br. J. Nutr. 2009, 101, 59–67. [Google Scholar] [CrossRef] [PubMed]
- Pereira, M.A.; Jacobs, D.R.; Van Horn, L.; Slattery, M.L.; Kartashov, A.I.; Ludwig, D.S. Dairy consumption, obesity, and the insulin resistance syndrome in young adults: The CARDIA study. JAMA 2002, 287, 2081–2089. [Google Scholar] [CrossRef] [PubMed]
- Appel, L.J.; Moore, T.J.; Obarzanek, E.; Vollmer, W.M.; Svetkey, L.P.; Sacks, F.M.; Bray, G.A.; Vogt, T.M.; Cutler, J.A.; Windhauser, M.M.; Lin, P.H.; Karanja, N. A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group. N. Engl. J. Med. 1997, 336, 1117–1124. [Google Scholar] [CrossRef] [PubMed]
- van Beresteijn, E.C.; van Schaik, M.; Schaafsma, G. Milk: Does it affect blood pressure? A controlled intervention study . J. Intern. Med. 1990, 228, 477–482. [Google Scholar] [PubMed]
- Buonopane, G.J.; Kilara, A.; Smith, J.S.; McCarthy, R.D. Effect of skim milk supplementation on blood cholesterol concentration, blood pressure, and triglycerides in a free-living human population. J. Am. Coll. Nutr. 1992, 11, 56–67. [Google Scholar] [PubMed]
- Hilary Green, J.; Richards, J.K.; Bunning, R.L. Blood pressure responses to high-calcium skim milk and potassium-enriched high-calcium skim milk. J. Hypertens. 2000, 18, 1331–1339. [Google Scholar] [CrossRef] [PubMed]
- Whelton, P.K.; He, J.; Cutler, J.A. Effects of oral potassium on blood pressure. Meta-analysis of randomized controlled clinical trials. JAMA 1997, 277, 1624–1632. [Google Scholar] [PubMed]
- Geleijnse, J.M.; Kok, F.J.; Grobbee, D.E. Blood pressure response to changes in sodium and potassium intake: A metaregression analysis of randomized trials. J. Hum. Hypertens. 2003, 17, 471–480. [Google Scholar] [CrossRef] [PubMed]
- van Mierlo, L.A.; Arends, L.R.; Streppel, M.T.; Zeegers, M.P.; Kok, F.J.; Grobbee, D.E.; Geleijnse, J.M. Blood pressure response to calcium supplementation: A meta-analysis of randomized controlled trials. J. Hum. Hypertens. 2006, 20, 571–580. [Google Scholar] [CrossRef] [PubMed]
- Obarzanek, E.; Velletri, P.A.; Cutler, J.A. Dietary protein and blood pressure. JAMA 1996, 275, 1598–1603. [Google Scholar] [PubMed]
- He, J.; Whelton, P.K. Effect of dietary fiber and protein intake on blood pressure: A review of epidemiological evidence. Clin. Exp. Hypertens. 1999, 21, 785–796. [Google Scholar] [CrossRef] [PubMed]
- Elliot, P.; Stamler, J.; Dyer, A.R.; Appel, L.; Dennis, B.; Kesteloot, H.; Ueshima, H.; Okayama, A.; Chan, Q.; Garside, D.B.; Zhou, B. Association between protein intake and blood pressure. The INTERMAP Study. Arch. Intern. Med. 2006, 166, 79–87. [Google Scholar] [CrossRef] [PubMed]
- Wang, Y.F.; Yancy, W.S.; Yu, D.; Champagne, C.; Appel, L.J.; Lin, P.H. The relationship between dietary protein intake and blood pressure: Results from the PREMIER study. J. Hum. Hypertens. 2008, 22, 745–754. [Google Scholar] [CrossRef] [PubMed]
- Burke, V.; Hodgson, J.M.; Beilin, L.J.; Giangiulioi, N.; Rogers, P.; Puddey, I.B. Dietary protein and soluble fiber reduce ambulatory blood pressure in treated hypertensives. Hypertension 2001, 38, 821–826. [Google Scholar] [CrossRef] [PubMed]
- Appel, L.J.; Carey, V.J.; Obarzanek, E.; Swain, J.F.; Miller, E.R.; Conlin, P.R.; Erlinger, T.P.; Rosner, B.A.; Laranjo, N.M.; Charleston, J.; McCarron, P.; Bishop, L.M.; OmniHeart Collaborative Research Group. Effects of protein, monounsaturated fat, and carbohydrate intake on blood pressure and serum lipids: Results of the OmniHeart randomized trial . JAMA 2005, 294, 2455–2464. [Google Scholar] [CrossRef] [PubMed]
- He, J.; Gu, D.; Wu, X.; Chen, J.; Duan, X.; Chen, J.; Whelton, P.K. Effect of soybean protein on blood pressure: A randomized, controlled trial. Ann. Intern. Med. 2005, 143, 1–9. [Google Scholar] [PubMed]
- Haug, A.; Hostmark, A.T.; Harstad, O.M. Bovine milk in human nutrition – a review. Lipids Health. Dis. 2007, 6, 25. [Google Scholar] [CrossRef] [PubMed]
- Pal, S.; Ellis, V. The chronic effects of whey proteins on blood pressure, vascular function, and inflammatory markers in overweight individuals . Obesity 2009. [Google Scholar]
- Phelan, M.; Aisling, A.; FitzGerald, R.J.; O’Brien, N.M. Casein-derived bioactive peptides: Biological effects, industrial uses, safety aspects and regulatory status. Int. Dairy J. 2009, 19, 643–654. [Google Scholar] [CrossRef]
- Gill, I.; López-Fandiño, R.; Jorba, X.; Vulfson, E.N. Biologically active peptides and enzymatic approaches to their production. Enzyme. Microb. Technol. 1996, 18, 163–183. [Google Scholar] [CrossRef] [PubMed]
- Chabance, B.; Marteau, P.; Rambaud, J.C.; Migliore-Samour, D.; Boynard, M.; Perrotin, P.; Guillet, R.; Jollès, P.; Fiat, A.M. Casein peptide release and passage to the blood in humans during digestion of milk and yoghurt. Biochimie 1998, 80, 155–165. [Google Scholar] [CrossRef] [PubMed]
- Parrot, S.; Degraeve, P.; Curia, C.; Martial-Gros, A. In vitro study on digestion of peptides in Emmental cheese: Analytical evaluation and influence on angiotensin I converting enzyme inhibitory peptides. Nahrung 2003, 47, 87–94. [Google Scholar] [CrossRef] [PubMed]
- Hernández-Ledesma, B.; Amigo, L.; Ramos, M.; Recio, I. Angiotensin converting enzyme inhibitory activity in commercial fermented products. Formation of peptides under simulated gastrointestinal digestion. J. Agric. Food Chem. 2004, 52, 1504–1510. [Google Scholar] [CrossRef] [PubMed]
- Shimizu, M. Food-derived peptides and intestinal functions. BioFactors 2004, 21, 43–47. [Google Scholar] [CrossRef] [PubMed]
- Christensen, J.E.; Dudley, E.G.; Pederson, J.A.; Steele, J.L. Peptidases and amino acid catabolism in lactic acid bacteria. Antonie van Leeuwenhoek 1999, 76, 2117–2146. [Google Scholar] [CrossRef]
- Juillard, V.; Guillot, A.; Le Bars, D.; Gripon, J.C. Specificity of milk peptide utilization by Lactococcus lactis. Appl. Environ. Microbiol. 1998, 64, 1230–1236. [Google Scholar] [PubMed]
- Nakamura, Y.; Yamamoto, N.; Sakai, K.; Okubo, A.; Yamazaki, S.: Takano. Purification and characterization of angiotensin I-converting enzyme inhibitors from sour milk . J. Dairy Sci. 1995, 78, 777–783. [Google Scholar] [PubMed]
- Nakamura, Y.; Yamamoto, N.; Sakai, K.; Takano, T. Antihypertensive effect of sour milk and peptides isolated from it that are inhibitors to angiotensin I-converting enzyme. J. Dairy Sci. 1995, 78, 1253–1257. [Google Scholar] [CrossRef] [PubMed]
- FitzGerald, R.J.; Murray, B.A. Bioactive peptides and lactic fermentations. Int. J. Dairy Technol. 2006, 59, 118–125. [Google Scholar] [CrossRef]
- Pihlanto-Leppälä, A.; Koskinen, P.; Piilola, K.; Tupasela, T.; Korhonen, H. Angiotensin I-converting enzyme inhibitory properties of whey protein digests: Concentration and characterization of active peptides. J. Dairy Res. 2000, 67, 53–64. [Google Scholar] [CrossRef] [PubMed]
- Wu, J.; Ding, X. Characterization of inhibition and stability of soy-protein derived angiotensin I-converting enzyme inhibitory peptides. Food Res. Int. 2002, 35, 367–375. [Google Scholar] [CrossRef]
- Minervini, F.; Algaron, F.; Rizzello, C.G.; Fox, P.F.; Monnet, V.; Gobbetti, M. Angiotensin I-converting-enzyme-inhibitory and antibacterial peptides from Lactobacillus helveticus PR4 proteinase-hydrolyzed caseins of milk from six species. Appl. Environ. Microbiol. 2003, 69, 5297–5305. [Google Scholar] [CrossRef] [PubMed]
- Korhonen, H.; Pihlanto, A. Food-derived bioactive peptides – Opportunities for designing future foods. Curr. Pharm. Des. 2003, 9, 1297–1308. [Google Scholar] [CrossRef] [PubMed]
- Korhonen, H.J. Milk-derived bioactive peptides: From science to applications. J. Functional Foods 2009, 1, 177–187. [Google Scholar] [CrossRef]
- Meyer, J.; Bütikofer, U.; Walther, B.; Wechsler, D.; Sieber, R. Hot topic: Changes in angiotensin-converting enzyme inhibition and concentrations of the tripeptides Val-Pro-Pro and Ile-Pro-Pro during ripening of different Swiss cheese varieties. J. Dairy Sci. 2009, 92, 826–836. [Google Scholar] [CrossRef] [PubMed]
- Yamamoto, N.; Maeno, M. Purification and characterization of an antihypertensive peptide from a yogurt-like product fermented by Lactobacillus helveticus CPN4 . J. Dairy Sci. 1999, 82, 1388–1393. [Google Scholar] [CrossRef] [PubMed]
- Yamamoto, N.; Akino, A.; Takano, T. Antihypertensive effect of the peptides derived from casein by an extracellular proteinase from Lactobacillus helveticus CP790. J. Dairy Sci. 1994, 77, 917–922. [Google Scholar] [CrossRef] [PubMed]
- Lehtinen, R.; Jauhiainen, T.; Kankuri, E.; Lindstedt, K.; Kovanen, P.T.; Kerojoki, O.; Korpela, R.; Vapaatalo, H. Effects of milk casein-derived tripeptides Ile-Pro-Pro, Val-Pro-Pro, and Leu-Pro-Pro on enzymes processing vasoactive precursors in vitro. Arzneim. Forsch/Drug Res. 2010, in press. [Google Scholar]
- Yamamoto, N.; Akino, A.; Takano, T. Antihypertensive effects of different kinds of fermented milk in spontaneously hypertensive rats. Biosci. Biotech. Biochem. 1994, 58, 776–778. [Google Scholar] [CrossRef]
- Nakamura, Y.; Masuda, O.; Takano, T. Decrease of tissue angiotensin I-converting enzyme activity upon feeding sour milk in spontaneously hypertensive rats. Biosci. Biotech. Biochem. 1996, 60, 488–489. [Google Scholar] [CrossRef]
- Sipola, M.; Finckenberg, P.; Santisteban, J.; Korpela, R.; Vapaatalo, H.; Nurminen, M.L. Long-term intake of milk peptides attenuates development of hypertension in spontaneously hypertensive rats. J. Physiol. Pharmacol. 2001, 52, 745–754. [Google Scholar] [PubMed]
- Sipola, M.; Finckenberg, P.; Korpela, R.; Vapaatalo, H; Nurminen, M.L. Effect of long-term intake of milk products on blood pressure in hypertensive rats . J. Dairy Res. 2002, 69, 103–111. [Google Scholar] [CrossRef] [PubMed]
- Jauhiainen, T.; Collin, M.; Narva, M.; Cheng, Z.J.; Poussa, T.; Vapaatalo, H; Korpela, R. Effect of long-term intake of milk peptides and minerals on blood pressure and arterial function in spontaneously hypertensive rats . Milchwissenschaft 2005, 60, 358–362. [Google Scholar]
- Jäkälä, P.; Pere, E; Lehtinen, R.; Turpeinen, A.; Korpela, R.; Vapaatalo, H. Cardiovascular activity of milk casein-derived tripeptides and plant sterols in spontaneously hypertensive rats . J. Physiol. Pharmacol. 2009, 60, 11–20. [Google Scholar] [PubMed]
- Jäkälä, P.; Hakala, A.; Turpeinen, A.; Korpela, R.; Vapaatalo, H. Casein-derived bioactive tripeptides Ile-Pro-Pro and Val-Pro-Pro attenuate the development of hypertension and improve endothelial function in salt-loaded Goto-Kakizaki rats . J. Functional Foods 2009, 1, 366–374. [Google Scholar]
- Jauhiainen, T.; Pilvi, T.; Cheng, Z.J.; Kautiainen, H.; Müller, D.N.; Vapaatalo, H.; Mervaala, E. Milk products containing bioactive tripeptides have an antihypertensive effect in double transgenic rats (dTGR) harbouring human renin and human angiotensinogen genes . J. Nutr. Metab. 2010. [Google Scholar]
- Masuda, O.; Nakamura, Y.; Takano, T. Antihypertensive peptides are present in aorta after oral administration of sour milk containing these peptides to spontaneously hypertensive rats. J. Nutr. 1996, 126, 3063–3068. [Google Scholar] [PubMed]
- Jäkälä, P.; Jauhiainen, T.; Korpela, R.; Vapaatalo, H. Milk protein-derived bioactive tripeptides Ile-Pro-Pro and Val-Pro-Pro protect endothelial function in vitro in hypertensive rats. J. Functional Foods 2009, 1, 266–273. [Google Scholar] [CrossRef]
- del Mar Contreras, M.; Carrón, R.; Montero, M.J.; Ramos, M.; Recio, I. Novel casein-derived peptides with antihypertensive activity. Int. Dairy J. 2009, 19, 566–573. [Google Scholar] [CrossRef]
- Quirós, A.; Ramos, M.; Muguerza, B.; Delgado, M.A.; Miguel, M.; Aleixandre, A.; Recio, I. Identification of novel antihypertensive peptides in milk fermented with Enterococcus faecalis. Int. Dairy J. 2007, 17, 33–41. [Google Scholar] [CrossRef]
- Antila, P.; Paakkari, I.; Järvinen, A.; Mattila, M.J.; Laukkanen, M.; Pihlanto-Leppälä, A.; Mäntsälä, P.; Hellman, J. Opioid peptides derived from in-vitro proteolysis of bovine whey proteins. Int. Dairy J. 1991, 1, 215–229. [Google Scholar] [CrossRef]
- Nurminen, M.L.; Sipola, M.; Kaarto, H.; Pihlanto-Leppälä, A.; Piilola, K.; Korpela, R.; Tossavainen, O.; Korhonen, H.; Vapaatalo, H. α-Lactorphin lowers blood pressure measured by radiotelemetry in normotensive and spontaneously hypertensive rats. Life Sci. 2000, 66, 1535–1543. [Google Scholar] [CrossRef] [PubMed]
- Sipola, M.; Finckenberg, P.; Vapaatalo, H.; Pihlanto-Leppälä, A.; Korhonen, H.; Korpela, R.; Nurminen, M.-L. Alpha-lactorphin and beta-lactorphin improve arterial function in spontaneously hypertensive rats . Life Sci. 2002, 71, 1245–1253. [Google Scholar] [CrossRef] [PubMed]
- Murakami, M.; Tonouchi, H.; Takahashi, R.; Kitazawa, H.; Kawai, Y.; Negishi, H.; Saito, T. Structural analysis of a new anti-hypertensive peptide (beta-lactosin B) isolated from a commercial whey product. J. Dairy Sci. 2004, 87, 1967–1974. [Google Scholar] [CrossRef] [PubMed]
- Abubakar, A.; Saito, T.; Kitazawa, H.; Kawai, Y.; Itoh, T. Structural analysis of new antihypertensive peptides derived from cheese whey protein by proteinase K digestion. J. Dairy Sci. 1998, 81, 3131–3138. [Google Scholar] [CrossRef] [PubMed]
- Marshall, K. Therapeutic applications of whey protein. Altern. Med. Rev. 2004, 9, 136–156. [Google Scholar] [PubMed]
- Saito, T. Antihypertensive peptides derived from bovine casein and whey proteins. Adv. Exp. Med. Biol. 2008, 606, 295–317. [Google Scholar] [PubMed]
- Pripp, A.H. Effect of peptides derived from food proteins on blood pressure: A meta-analysis of randomized controlled trials . Food Nutr. Res. 2008, 52. [Google Scholar]
- Xu, J.Y.; Qin, L.Q.; Wang, P.Y.; Li, W.; Chang, C. Effect of milk tripeptides on blood pressure: A meta-analysis of randomized controlled trials. Nutrition 2008, 24, 933–940. [Google Scholar] [CrossRef] [PubMed]
- Engberink, M.F.; Schouten, E.G.; Kok, F.J.; van Mierlo, L.A.J.; Brouwer, I.A.; Geleijnse, J.M. Lactotripeptides show no effect on human blood pressure. Results from a double-blind randomized controlled trial. Hypertension 2008, 51, 399–405. [Google Scholar] [CrossRef] [PubMed]
- van der Zander, K.; Bots, M.L.; Bak, A.A.A.; Koning, M.M.G.; de Leeuw, P.W. Enzymatically hydrolyzed lactotripeptides do not lower blood pressure in mildly hypertensive subjects. Am. J. Clin. Nutr. 2008, 88, 1697–1702. [Google Scholar] [CrossRef] [PubMed]
- van der Zander, K.; Jakel, M.; Bianco, V.; Koning, M.M. Fermented lactotripeptides-containing milk lowers daytime blood pressure in high normal-to-mild hypertensive subjects. J. Hum. Hypertens. 2008, 22, 804–806. [Google Scholar] [CrossRef] [PubMed]
- de Leeuw, P.W.; van der Zander, K.; Kroon, A.A.; Rennenberg, R.M.; Koning, M.M. Dose-dependent lowering of blood pressure by dairy peptides in mildly hypertensive subjects. Blood Press. 2009, 18, 44–50. [Google Scholar] [CrossRef] [PubMed]
- Nakamura, T.; Mizutani, J.; Sasaki, K.; Yamamoto, N.; Takazawa, K. Beneficial potential of casein hydrolysate containing Val-Pro-Pro and Ile-Pro-Pro on central blood pressure and hemodynamic index: A preliminary study . J. Med. Food 2009. [Google Scholar]
- Yoshizawa, M.; Maeda, S.; Miyaki, A.; Misono, M.; Choi, Y.; Shimojo, N.; Ajisaka, R.; Tanaka, H. Additive beneficial effects of lactotripeptides and aerobic exercise on arterial compliance in postmenopausal women. Am. J. Physiol. Heart. Circ. Physiol. 2009, 297, 1899–1902. [Google Scholar] [CrossRef]
- Turpeinen, A.M.; Kumpu, M.; Rönnback, M.; Seppo, L.; Kautiainen, H.; Jauhiainen, T.; Vapaatalo, H.; Korpela, R. Antihypertensive and cholesterol-lowering effects of a spread containing bioactive peptides IPP and VPP and plant sterols. J. Functional Foods 2009, 1, 260–265. [Google Scholar] [CrossRef]
- van Mierlo, L.A.J.; Koning, M.M.G.; van der Zander, K.; Draijer, R. Lactotripeptides do not lower blood pressure in untreated whites: Results from 2 controlled multicenter crossover studies. Am. J. Clin. Nutr. 2009, 89, 617–623. [Google Scholar] [CrossRef] [PubMed]
- Kajimoto, O.; Aihara, K.; Hirata, H.; Takahashi, R.; Nakamura, Y. Hypotensive effects of tablets containing “lactotripeptides (VPP, IPP)”. J. Nutr. Food 2001, 4, 51–61. [Google Scholar]
- Seppo, L.; Kerojoki, O.; Suomalainen, T.; Korpela, R. The effect of a Lactobacillus helveticus LBK-16H fermented milk on hypertension – a pilot study on humans. Milchwissenschaft 2002, 57, 124–127. [Google Scholar]
- Nakamura, Y.; Kajimoto, O.; Kaneko, K.; Aihara, K.; Mizutani, J.; Ikeda, N.; Nishimura, A.; Kajimoto, Y. Effects of the liquid yogurts containing “lactotripeptide (VPP, IPP)” on high-normal blood pressure. J. Nutr. Food 2004, 7, 123–137. [Google Scholar]
- Aihara, K.; Kajimoto, O.; Hirata, H.; Takahashi, R.; Nakamura, Y. Effect of powdered milk fermented with Lactobacillus helveticus on subjects with high-normal blood pressure or mild hypertension. J. Am. Coll. Nutr. 2005, 24, 257–265. [Google Scholar] [PubMed]
- Mizuno, S.; Matsuura, K.; Gotou, T.; Nishimura, S.; Kajimoto, O.; Yabune, M.; Kajimoto, Y.; Yamamoto, N. Antihypertensive effect of casein hydrolysate in a placebo-controlled study in subjects with high-normal blood pressure and mild hypertension. Br. J. Nutr. 2005, 94, 84–91. [Google Scholar] [CrossRef] [PubMed]
- Hirota, T.; Ohki, K.; Kawagishi, R.; Kajimoto, Y.; Mizuno, S.; Nakamura, Y.; Kitakaze, M. Casein hydrolysate containing the antihypertensive tripeptides Val-Pro-Pro and Ile-Pro-Pro improves vascular endothelial function independent of blood pressure-lowering effects: Contribution of the inhibitory action of angiotensin-converting enzyme. Hypertens. Res. 2007, 30, 489–496. [Google Scholar] [CrossRef] [PubMed]
- Sano, J.; Ohki, K.; Higuchi, T.; Aihara, K.; Mizuno, S.; Kajimoto, O.; Nakagawa, A.; Kajimoto, Y.; Nakamura, Y. Effect of casein hydrolysate, prepared with protease derived from Aspergillus oryzae, on subjects with high-normal blood pressure or mild hypertension. J. Med. Food 2005, 8, 423–430. [Google Scholar] [CrossRef]
- Jauhiainen, T.; Vapaatalo, H.; Poussa, T.; Kyrönpalo, S.; Rasmussen, M.; Korpela, R. Lactobacillus helveticus fermented milk lowers blood pressure in hypertensive subjects in 24-h ambulatory blood pressure measurement. Am. J. Hypertens. 2005, 18, 1600–1605. [Google Scholar] [CrossRef] [PubMed]
- Boelsma, E.; Kloek, J. Lactotripeptides and antihypertensive effects: A critical review. Br. J. Nutr. 2009, 101, 776–786. [Google Scholar] [CrossRef] [PubMed]
- Pins, J.J.; Keenan, J.M. Effects of whey peptides on cardiovascular disease risk factors. J. Clin. Hypertens. (Greenwich), 2006, 8, 775–782. [Google Scholar] [CrossRef]
- Lee, Y.M.; Skurk, T.; Hennig, M.; Hauner, H. Effect of a milk drink supplemented with whey peptides on blood pressure in patients with mild hypertension. Eur. J. Nutr. 2007, 46, 21–27. [Google Scholar] [CrossRef] [PubMed]
- Miguel, M.; Dávalos, A.; Manso, M.A.; de la Peña, G.; Lasunción, M.A.; López-Fandiño, R. Transepithelial transport across Caco-2 cell monolayers of antihypertensive egg-derived peptides. PepT1-mediated flux of Tyr-Pro-Ile. Mol. Nutr. Food Res. 2008, 12, 1507–1513. [Google Scholar] [CrossRef]
- Foltz, M.; Cerstiaens, A.; van Meensel, A.; Mols, R.; van der Pijl, P.C.; Duchateau, G.S.M.J.E. The angiotensin converting enzyme inhibitory tripeptides Ile-Pro-Pro and Val-Pro-Pro show increasing permeabilities with increasing physiological relevance of absorption models . Peptides 2008, 29, 1312–1320. [Google Scholar] [CrossRef] [PubMed]
- Foltz, M.; Meynen, E.E.; Bianco, V.; van Platerink, C.; Koning, T.M.M.G.; Kloek, J. Angiotensin converting enzyme inhibitory peptides from a lactotripeptide-enriched milk beverage are absorbed intact into the circulation. J. Nutr. 2007, 137, 953–958. [Google Scholar] [PubMed]
- van der Pijl, P.C.; Kies, A.K.; Ten Have, G.A.M.; Duchateau, G.S.M.J.E.; Deutz, N.E.P. Pharmacokinetics of proline-rich tripeptides in the pig. Peptides 2008, 29, 2196–2202. [Google Scholar] [CrossRef] [PubMed]
- Vanhoof, G.; Goossens, F.; De Meester, I.; Hendriks, D.; Scharpé, S. Proline motifs in peptides and their biological processing. FASEB J. 1995, 9, 736–744. [Google Scholar] [PubMed]
- Jauhiainen, T.; Wuolle, K.; Vapaatalo, H.; Kerojoki, O.; Nurmela, K.; Lowrie, C.; Korpela, R. Oral absorption, tissue distribution and excretion of a radiolabelled analog of a milk-derived antihypertensive peptide, Ile-Pro-Pro, in rats. Int. Dairy J. 2007, 17, 1216–1223. [Google Scholar] [CrossRef]
- Dolan, E.; Thijs, L.; Li, Y.; Atkins, N.; McCormack, P.; McClory, S.; O’Brien, E.; Staessen, J.A.; Stanton, A.V. Ambulatory arterial stiffness index as a predictor of cardiovascular mortality in the Dublin Outcome Study. Hypertension 2006, 47, 365–370. [Google Scholar] [CrossRef] [PubMed]
- Chirinos, J.A.; Zambrano, J.P.; Chakko, S.; Veerani, A.; Schob, A.; Willens, H.J.; Perez, G.; Mendez, A.J. Aortic pressure augmentation predicts adverse cardiovascular events in patients with established coronary artery disease. Hypertension 2005, 45, 980–985. [Google Scholar] [CrossRef] [PubMed]
- Jauhiainen, T.; Rönnback, M.; Vapaatalo, H.; Wuolle, K.; Kautiainen, H.; Korpela, R. Lactobacillus helveticus fermented milk reduces arterial stiffness in hypertensive subjects. Int. Dairy J. 2007, 17, 1209–1211. [Google Scholar] [CrossRef]
- Jauhiainen, T. Blood pressure lowering effects of Lactobacillus helveticus fermented milk containing bioactive peptides Ile-Pro-Pro and Val-Pro-Pro: Mechanistic, Kinetic and Clinical Studies . University of Helsinki, Faculty of Medicine, Institute of Biomedicine: Helsinki, 2007; Doctoral dissertation. [Google Scholar]
- Yamaguchi, N.; Kawaguchi, K.; Yamamoto, N. Study of the mechanism of antihypertensive peptide VPP and IPP in spontaneously hypertensive rats by DNA microarray analysis. Eur. J. Pharmacol. 2009, 620, 71–77. [Google Scholar] [CrossRef] [PubMed]
- De Gennaro, C.V.; Rossoni, G.; Rigamonti, A.; Bonomo, S.; Manfredi, B.; Berti, F.; Muller, E. Enalapril and quinapril improve endothelial vasodilator function and aortic eNOS gene expression in L-NAME-treated rats. Eur. J. Pharmacol. 2002, 450, 61–66. [Google Scholar] [CrossRef] [PubMed]
- Rummery, N.M.; Grayson, T.H.; Hill, C.E. Angiotensin-converting enzyme inhibition restores endothelial but not medial connexin expression in hypertensive rats. J. Hypertens. 2005, 23, 317–328. [Google Scholar] [CrossRef] [PubMed]
- Fyhrquist, F.; Saijonmaa, O. Renin-angiotensin system revisited. J. Intern. Med. 2008, 264, 224–236. [Google Scholar] [CrossRef] [PubMed]
- Wei, L.; Clauser, E.; Alhenc-Gelas, F.; Corvol, P. The two homologous domains of human angiotensin I-converting enzyme interact differently with competitive inhibitors. J. Biol. Chem. 1992, 267, 13398–13405. [Google Scholar] [PubMed]
- Natesh, R.; Schwager, S.L.U.; Sturrock, E.D.; Acharya, K.R. Crystal structure of the human angiotensin-converting enzyme-lisinopril complex. Nature 2003, 421, 551–554. [Google Scholar] [CrossRef] [PubMed]
- Meisel, H. Biochemical properties of peptides encrypted in bovine milk proteins. Curr. Med. Chem. 2005, 12, 1905–1919. [Google Scholar] [CrossRef] [PubMed]
- Wuerzner, G.; Peyrard, S.; Blanchard, A.; Lalanne, F.; Azizi, M. The lactotripeptides isoleucine-proline-proline and valine-proline-proline do not inhibit the N-terminal or C-terminal angiotensin converting enzyme active sites in humans. J. Hypertens. 2009, 27, 1404–1409. [Google Scholar] [CrossRef] [PubMed]
- Pripp, A.H.; Isaksson, T.; Stepaniak, L.; Sørhaug, T. Quantitative structure-activity relationship modelling of ACE-inhibitory peptides derived from milk proteins. Eur. Food Res. Technol. 2004, 219, 579–583. [Google Scholar] [CrossRef]
- Wu, J.; Aluko, R.E.; Nakai, S. Structural requirements of angiotensin I-converting enzyme inhibitory peptides: Quantitative structure-activity relationship study of di- and tripeptides. J. Agric. Food Chem. 2006, 54, 732–738. [Google Scholar] [CrossRef] [PubMed]
- Foltz, M.; van Buren, L.; Klaffke, W.; Duchateau, G.S.M.J.E. Modeling of the relationship between dipeptide structure and dipeptide stability, permeability, and ACE-inhibitory activity . J. Food Sci. 2009, 74, 243–251. [Google Scholar] [CrossRef]
- FDA GRAS Substances (SCOGS) Database 2006. Available online: http://www.fda.gov/Food/FoodIngredients Packaging/GenerallyRecognizedasSafeGRAS/GRASSubstancesSCOGSDatabase/default.htm/ accessed 30 December 2009.
- Commission regulation (EC) No 983/2009. In OJEU; 2009; pp. L277:3–L277:8.
- Piepho, R.W. Overview of the angiotensin-converting-enzyme inhibitors. Am. J. Health Syst. Pharm. 2000, 57, 3–7. [Google Scholar]
- Pryde, P.G.; Sedman, A.B.; Nugent, C.E.; Barr, M. Angiotensin-converting enzyme inhibitor fetopathy. J. Am. Soc. Nephrol. 1993, 3, 1575–1582. [Google Scholar] [PubMed]
- Quan, A. Fetopathy associated with exposure to angiotensin converting enzyme inhibitors and angiotensin receptor antagonists. Early Hum. Dev. 2006, 82, 23–28. [Google Scholar] [CrossRef] [PubMed]
- Maeno, M.; Nakamura, Y.; Mennear, J.H.; Bernard, B.K. Studies of the toxicological potential of tripeptides (L-valyl-L-prolyl-L-proline and L-isoleucyl-L-prolyl-L-proline): III. Single- and/or repeated-dose toxicity of tripeptides-containing Lactobacillus helveticus-fermented milk powder and casein hydrolysate in rats. Int. J. Toxicol. 2005, 24, 13–23. [Google Scholar] [CrossRef] [PubMed]
- Dent, M.P.; O’Hagan, S.; Braun, W.H.; Schaetti, P.; Marburger, A.; Vogel, O. A 90-day subchronic toxicity study and reproductive toxicity studies on ACE-inhibiting lactotripeptide. Food Chem. Toxicol. 2007, 45, 1468–1477. [Google Scholar] [CrossRef] [PubMed]
- Ponstein-Simarro Doorten, A.Y.; vd Wiel, J.A.G.; Jonker, D. Safety evaluation of an IPP tripeptide-containing milk protein hydrolysate. Food Chem. Toxicol. 2009, 47, 55–61. [Google Scholar] [CrossRef] [PubMed]
- Corrigendum to Regulation (EC) No 1924/2006 of the European Parliament and of the Council of 20 December 2006 on nutrition and health claims on foods. In OJEU; 2007; pp. L12:3–L12:18. Available online: http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L: 2007:012:00 03:0018:EN:PDF/ accessed 19 January 2010.
© 2010 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
Share and Cite
Jäkälä, P.; Vapaatalo, H. Antihypertensive Peptides from Milk Proteins. Pharmaceuticals 2010, 3, 251-272. https://doi.org/10.3390/ph3010251
Jäkälä P, Vapaatalo H. Antihypertensive Peptides from Milk Proteins. Pharmaceuticals. 2010; 3(1):251-272. https://doi.org/10.3390/ph3010251
Chicago/Turabian StyleJäkälä, Pauliina, and Heikki Vapaatalo. 2010. "Antihypertensive Peptides from Milk Proteins" Pharmaceuticals 3, no. 1: 251-272. https://doi.org/10.3390/ph3010251
APA StyleJäkälä, P., & Vapaatalo, H. (2010). Antihypertensive Peptides from Milk Proteins. Pharmaceuticals, 3(1), 251-272. https://doi.org/10.3390/ph3010251