Milk protein peptides with angiotensin I-Converting enzyme inhibitory (ACEI) activity

Critical Reviews in Food Science and Nutrition

Volumn 50, Issue 5, 2010, Pages 390-402

  Ricci, Ignacio ^a   Artacho, Reyes ^a   Olalla, Manuel ^a  

^a UNIVERSITY OF GRANADA   (Spain)

Author keywords

Angiotensin I converting enzyme inhibitory (ACEI) activity peptide; Antihypertensive effect; Milk bioactive peptides

Indexed keywords

DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; MILK PROTEIN;

ARTICLE; BLOOD PRESSURE; CHEMISTRY; HUMAN; HYPERTENSION;

ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; BLOOD PRESSURE; HUMANS; HYPERTENSION; MILK PROTEINS;

ANIMALIA;

EID: 77950871987     PISSN: 10408398     EISSN: 15497852     Source Type: Journal    
DOI: 10.1080/10408390802304198     Document Type: Article

References (112)

1. Abubakar, A., Tadao, S., Kitazawa, H., Kawai, Y. and Itoh, T. (1998). Structural analysis of new antihypertensive peptides derived from cheese whey protein by proteinase K digestion. J. Dairy Sci. 81:3131-3138.
2. Adessi, C. and Soto, C. (2002). Converting a peptide into a drug: strategies to improve stability and bioavailability. Curr. Med. Chem. 9:963-978.
3. Araujo, M. C., Melo, R. L., Cesari, M. H. and Juliano, M. A. (2000). Peptidase specificity characterization of C- and N-terminal catalytic sites of angiotensin I-converting enzyme. Biochemistry. 39:8519-8525.
4. Bitri, L. (2004). Optimization study for the production of an opioid-like preparation from bovine casein by mild acidic hydrolysis. Int. Dairy J. 14:535-539.
5. Chen, G.-W., Tsai, J.-S. and Pan B.-S. (2007). Purification of angiotensin I- converting enzyme inhibitory peptides and antihypertensive effect of milk produced by protease-facilitated lactic fermentation. Int. Dairy J. 17:641- 647.
6. Cheung, H.-S., Feng-Lai, W., Ondetti, M. A., Sabo, E. F. and Cushman, D. W. (1980). Binding of peptide substrates and inhibitors of angiotensin- converting-enzyme. J. Biol. Chemistr. 255:401-407.
7. Conlin, P. R. (2001). Efficacy and safety of angiotensin receptor blockers: A review of Losartan in essential hypertension. Current Ther. Res. 62:79-91.
8. Conlin, P. R., Chow, D., Miller, E. R., Svetkey, L. P., Lin, P. H., Harsha, D. W., Moore, T. J., Sacks, F. M. and Appel, L. J. (2000). The effect of dietary patterns on blood pressure control in hypertensive patients: results from the Dietary Approaches to Stop Hypertension (DASH) trial. Am. J. Hyperten. 13:949-955.
9. Desai, P., Coutinho, E., and Srivastava, S. (2002). Conformational diversity of T-kinin in DMSO, water and HFA. E. J. Medic. Chemistr. 37:135-146.
10. Deszi, L. (2000). Fibrinolytic actions of ACE inhibitors: a significant plus beyond antihypertensive therapeutic effects. Cardio. Res. 47:642-644.
11. Fiat, A. M., Migliore-Samour, D., Jolles, P., Drouet, L., Bal dit Sollier, C. and Caen, J. (1993). Biologically active peptides from milk proteins with emphasis on two examples concerning antithrombotic and immunomodulating activities. J. Dairy Sci. 76:301-10.
12. FitzGerald, R. J., Murray, B. A. and Walsh, D. J. (2004). Hypotensive peptides from milk proteins. J. Nutr. 134:980-988.
13. Fuglsang, A., Nilsson, D. and Nyborg, N. (2002). Cardiovascular effects of fermented milk containing angiotensin-converting enzyme inhibitors evaluated in permanently cathereterized spontaneously hypertensive rats. Appl. Envir. Microbiol. 68:3566-3569.
14. Gardner, M. L. (1988). Gastrointestinal absorption of intact proteins. Annu. Rev. Nutr. 8:329-350.
15. Geerlings, A., Villar, I. C., Zarco, F. H., Sánchez, M., Vera, R., Gomez, A. Z., Boza, J. and Duarte, J. (2006). Identification and characterization of novel angiotensin-converting enzyme inhibitors obtained from goat milk. J. Dairy Sci. 89:3326-35.
16. Gobbetti, M., Ferranti, P., Smacchi, E., Goffredi, F. and Addeo, F. (2000). Production of angiotensin-I-converting enzyme inhibitory peptides in fermented milks started by Lactobacillus delbruekii subsp. bulgaricus SS1 and Lactococcus lactis subsp cremoris FT4. Appl. Envir. Microbiol. 66:3898-3904.
17. Gobbetti, M., Stepaniak, L., De Angelis, M., Corsetti, A. and Di Cagno, R. (2002). Latent bioactive peptides in milk proteins: proteolytic activation and significance in dairy processing. Crit. Rev. Food Sci. Nutr. 42:223-239.
18. Gómez-Ruiz, J. A., Ramos, M. and Recio, I. (2002). Angiotensin-converting enzyme-inhibitory peptides in manchego cheeses manufactured with different starter cultures. Int. Dairy J. 12:697-706.
19. Gómez-Ruiz, J. A., Recio, I. and Belloque, J. (2004). ACE-inhibitoryactivity and structural properties of peptide Asp-Lys-Ile-His-Pro [b- CN f(47-51)]. Study of the peptide forms synthesized by different methods. J. Agric. Food Chem. 52:6315-6319.
20. Hartmann, R. and Meisel, H. (2007). Food-derived peptides with biological activity: from research to food applications. Curr. Opinion Biotech. 18:163-169.
21. Hata, Y., Yamamoto, M., Ohni, M., Nakajima, K., Nakamura, Y., and Takano, T. (1996). A placebo-controlled study of the effect of sour milk on blood pressure in hypertensive subjects. Am. J. Clin. Nutr. 64:767-771.
22. Hayes, M., Ross, R. P., Fitzgerald, G. F. and Stanton, C. (2007a). Putting microbes to work: dairy fermentation, cell factories and bioactive peptides. Part I: overview. Biotechnol J. 2:426-34.
23. Hayes, M., Stanton, C., Fitzgerald, G. F. and Ross, R. P. (2007b). Putting microbes to work: Dairy fermentation, cell factories and bioactive peptides. Part II: Bioactive peptide functions. Biotechnol. J. 2:435-449.
24. Hayes, M., Stanton, C., Slattery, H., O'Sullivan, O., Hill, C., Fitzgerald, G. F. and Ross, R. P. (2007c). Casein fermentate of Lactobacillus animalis DPC6134 contains a range of novel propeptide angiotensin-converting enzyme inhibitors. Appl. Environ. Microbiol. 14:4658-4667.
25. Hernández-Ledesma, B., Amigo, L., Ramos, M. and Recio, I. (2004). Angiotensin converting enzyme inhibitory activity in commercial fermented products. Formation of peptides under simulated gastrointestinal digestión. J. Agric. Food Chem. 52:1504-1510.
26. Hernández-Ledesma, B., Miguel, M., Amigo, L., Aleixandre, M. A. and Recio, I. (2007a). Effect of simulated gastrointestinal digestion on the antihypertensive properties of synthetic β-lactoglobulin peptide sequences. J. Dairy Res.74:336-339.
27. Hernández-Ledesma, B., Quirós, A., Amigo, L. and Recio, I. (2007b). Identification of bioactive peptides after digestion of human milk and infant formula with pepsin and pancreatin. Int. Dairy J. 17:42-49.
28. Hernández-Ledesma, B., Miralles, B., Amigo, L., Ramos, M. and Recio, I. (2005). Identification of antioxidant and ACE-inhibitory peptides in fer- mented milk. J. Sci. Food Agric. 85:1041-1048.
29. Hernández-Ledesma, B., Ramos, M., Recio, I. and Amigo, L. (2006). Effect of β-lactoglobulin hydrolysis with thermolysin under denaturing temperatures on the release of bioactive peptides. J. Chromatogr. 1116:31-37.
30. Hernández-Ledesma, B., Recio, I., Ramos, M. and Amigo, L. (2002). Preparation of ovine and caprine b-lactoglobulin hydrolysates with ACE-inhibitory activity. Identification of active peptides from caprine b-lactoglobulin hydrol-ysed with thermolysin. Int. Dairy J. 12:805-812.
31. Hirota, T., Ohki, K., Kawagishi, R., Kajimoto, Y., Mizuno, S., Nakamura, Y. and Kitakaze, M. (2007). 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. Hipertens. Res. 30:6.
32. Ishikawa-Takata, K., Ohta, T. and Tanaka, H. (2003). How much exercise is required to reduce blood pressure in essential hypertensives: a dose-response study. Am. J. Hyperten. 16:629-633.
33. Itakura, H., Ikemoto, S., Terada, S. and Kondo, K. (2001). The effect of sour milk on blood pressure in untreated hypertensive and normotensive subjects. J. Jpn. Soc. Nutr. Food Sci. 23:26-31.
34. Jauhiainen, T. and Korpela, R. (2007). Milk peptides and blood pressure. J. Nutr. 137:825-829.
35. Jauhiainen, T., Collin, M., Narva, M., Poussa, T. and Korpela, R. (2005a). Effect of long term intake of milk peptides and minerals on blood pressure and arterial function in spontaneously hypertensive rats. Milchwissenschaft. 60:358-363.
36. Jauhiainen, T., Vapaatalo, H., Poussa, T., Kyronpalo, S., Rasmussen, M. and Korpela, R. (2005b). Lactobacillus helveticus fermented milk lowers blood pressure in hypertensive subjects in 24h ambulatory blood preassure measurement. Am J Hypertens. 18:1600-1605.
37. Kajimoto, O., Kotaro, A., Hirata, H., Takahashi, R. and Nakamura, Y. (2001a). Hipotensive effects of the tablets containing "Lactotripeptides" (VPP, IPP). J. Nutr. Food. 4:51-61.
38. Kajimoto, O., Kurosaki, T., Mizutani, J., Ikeda, N., Kaneko, K., Aihara, K., Yabune, M. and Nakamura, Y. (2002). Antihypertensive effects of liquid yogurts containing "lactotripeptides (VPP, IPP)" in mild hypertensive subjects. J. Nutr. Food. 5:55-66.
39. Kajimoto, O., Nakamura, Y., Yada, H., Moriguchi, S., Hirata, H., and Takahashi, T. (2001b). Hypotensive effects of sour milk in subjects with mild or moderate hypertension. J. Jpn. Soc. Nutr. Food Sci. 54:347-354.
40. Kilara, A. and Panyam, D. (2003). Peptides from milk proteins and their properties. Crit. Rev. Food Sci. Nutr. 43:607-633.
41. Kitts, D. D. and Weiler, K. (2003). Bioactive proteins and peptides from food sources. Applications of bioprocesses used in isolation and recovery. Curr. Pharmacol. Design. 9:1309-1323.
42. Korhonen, H. and Pihlanto-Leppala, A. (2006). Food-derived bioactive peptides: opportunities for designing future foods. Curr. Pharm. Des. 9:1297-1308.
43. Korhonen, H. and Pihlanto-Leppala, A. (2007). Technological options for the production of health-promoting proteins and peptides derived from milk and colostrum. Curr. Pharm. Des. 13:829-43.
44. Korhonen, H. and Pihlanto, A. (2003a). Bioactive peptides: Novel applications for milk proteins. Appl. Biotechnol. Food Sci. Policy. 1:133-144.
45. Korhonen, H. and Pihlanto, A. (2003b). Food-derived bioactive peptides-Opportunities for designing future foods. Curr. Pharm. Des. 9:1297-1308.
46. Leclerc, P. -L., Gauthier, S. F., Bachelard, H., Santure, M. and Roy, D. (2002). Antihypertensive activity of casein-enriched milk fermented by Lactobacillus helveticus. Int. Dairy J. 12:995-1004.
47. Lee, Y., Skurk, T., Hennig, M. and Hauner, H. (2007). Effect of a milk drink supplemented with whey peptides on blood pressure in patients with mild hipertension. Eur. J. Nutr. 46:21-27.
48. Li, E. W. Y. and Mine, Y. (2004). Immunoenhancing effects of bovine gly-comacropeptide and its derivatives on the proliferative response and phagocytic activities of human macrophagelike cells, U937. J. Agric. Food Chem. 52:2704-2708.
49. Li, G. H., Liu, H., Shi, Y. H. and Le, G. W. (2005). Direct spectrophotometric measurement of angiotensin I-converting enzyme inhibitory activity for screening bioactive peptides. J. Pharm. Biomed. Anal. 37:219-224.
50. Liu, D., Sun, H., Zhang, K. and Li, S. (2007). High-level expression of milk-derived antihypertensive peptide in Escherichia coli and its bioactivity. J. Agric. Food Chem. 55:5109-5112.
51. López Expósito, I. and Recio, I. (2006). Antibacterial activity of peptides and folding variants from milk proteins. Int. Dairy J. 16:1294-1305.
52. López-Fandiño, R., Otte, J. and Van Camp, J. (2006). Physiological, chemical and technological aspects of milk-protein-derived peptides with antihypertensive and ACE-inhibitory activity. Int. Dairy J. 16:1277-1293.
53. Losacco M., Gallerani R., Gobbetti M., Minervini F. and De Leo, F. (2007). Production of active angiotensin-I converting enzyme inhibitory peptides derived from bovine beta-casein by recombinant DNA technologies. Biotechnol. J. 2:1425-34.
54. Maeno, M., Yamamoto, N. and Takano, T. (1996). Identification of antihy-pertensive peptides from casein hydrolysate produced by a proteinase from Lactobacillus helveticus CP790. J. Dairy Sci. 73:1316-1321.
55. Malkoski, M., Dashper, S. G., O'Brien-Simpson, N. -M., Talbo, G. H., Macris, M., Cross, K. J. and Reynolds, E. C. (2001). Kappacin, a novel antibacterial peptide from bovine milk. Antimicrobial A. Chemot. 45:2309-2315.
56. Manso, M. A. and López-Fandino, R. (2004). κ-Casein macropeptides from cheese whey: Physicochemical, biological, nutritional, and technological features for possible uses. Food Rev. Int. 20:329-355.
57. Matar, C., Valdez, J. C., Medina, M., Rachid M. and Perdigón, G. (2001). Immunomodulating effects of milks fermented by Lactobacillus helveticus and its non-proteolytic variant. J. Dairy Res. 68:601-609.
58. McCann, K. B., Shiell, B. J., Michalski, W. P., Lee, A., Wan, J. and Roginski, H. (2005). Isolation and characterization of antibacterial peptides derived from the f(164-207) region of bovine as2-casein. Int. Dairy J. 15:133-143.
59. McCann, K. B., Shiell, B. J., Michalski, W. P., Lee, A., Wan, J. and Roginski, H. (2006). Isolation and characterization of a novel antibacterial peptide from bovine as1-casein. Int. Dairy J. 16:316-323.
60. Meisel H. and FitzGerald R. J. (2003). Biofunctional peptides from milk proteins: mineral binding and cytomodulatory effects. Curr. Pharm. Des. 9:1289-95.
61. Meisel, H. (2004). Multifunctional peptides encrypted in milk proteins. BioFactor. 21:55-61.
62. Meisel, H. (2005). Biochemical properties of peptides encrypted in bovine milk proteins. Curr. Med. Chem. 12:1905-1919.
63. Meisel, H. and Bockelmann, W. (1999). Bioactive peptides encrypted in milk proteins: proteolytic activation and thropho-functional properties. Ant. Van Leeuwen. 76:207-215.
64. Meisel, H., Bernard, H., Fairweather-Tait, S., FitzGerald, R. J., Hartmann, R., Lane, C. N., McDonagh, D., Teucher, B. and Wal, J. M. (2003). Detection of caseinophosphopeptides in the distal ileostomy fluid of human subjects. Brit. J. Nutr. 89:351-358.
65. Mellander, O. (1950). The physiological importance of the casein phosphopeptide calcium salts. II. Peroral calcium dosage of infants. Acta Soc. Med. Ups. 55:247-255.
66. Miguel, M., Manso, M., Aleixandre, A., Alonso, M. J., Salaices, M. and López-Fandiño, R. (2007). Vascular effects, angiotensin I- converting enzyme (ACE)-inhibitory activity, and antihypertensive properties of peptides derived from egg white. J. Agric. Food Chem. 5:10615-21.
67. Miguel, M., Muguerza, B., Sánchez, E., Delgado, M. A., Recio, I. and Ramos, M. (2005). Long-term blood pressure-lowering effect of milk fermented by Enterococcus faecalis CECT 5728 in spontaneously hypertensive rats. Brit. J. Nutr. 93:1-9.
68. Minervini, F., Algaron, F., Rizzello, C. G. P., Fox, F., Monnet, V. and Gobbetti, M. (2003). Angiotensin I-converting-enzyme-inhibitory and antibacterial peptides from Lactobacillus helveticus PR4 proteinase-hydrolyzed caseins of milk from six species. Appl. Envir. Microbiol. 69:5297-5305.
69. Mizuno, S., Matsuura, K., Gotou, T., Nishimura, S., Kajimoto, O. and Yabune, M. (2005). Antihypertensive effect of casein hydrolysate in a placebo-controlled study in subjects with high-normal blood pressure and mild hypertension. Brit. J. Nutr. 94:84-91.
70. Mizushima, S., Ohshige, K., Watanabe, J., Kimura, M., Kadowaki, T. and Nakamura, Y. (2004). Randomized controlled trial of sour milk on blood pressure in borderline hypertensive men. Am. J. Hypertens. 17:701-706.
71. Muguerza, B., Ramos, M., Sánchez, E., Manso, M. A., Miguel, M., Aleixandre, A., Delgado, M. A. and Recio, I. (2006). Antihypertensive activity of milk fermented by Enterococcus faecalis strains isolated from raw milk. Int. Dairy J. 16:61-69.
72. Mullally, M. M., Meisel, H. and Fitzgerald, R. J. (1996). Synthetic peptides corresponding to α-lactalbumin and β-lactoglobulin sequences with angiotensin- I- converting enzyme inhibitory activity. Biol. Chem. Hoppe-Seyler. 377:259-260.
73. Mullally, M. M., Meisel, H. and Fitzgerald, R. J. (1997). Identification of a novel angiotensin-I-converting enzyme inhibitory peptide corresponding to a triptic fragment of bovine β-lactoglobulin. FEBS Letters. 402:99-101.
74. Murakami, M., Tonouchi, H., Takahashi, R., Kitazawa, H., Kawai, Y., Negishi, H. and Saito, T. (2004). Structural analysis of a new anti-hypertensive peptide (β-Lactosin B) isolated from a commercial whey product. J. Dairy Sci. 87:1967-1974.
75. Murray B. A. and FitzGerald R. J. (2007). Angiotensin converting enzyme inhibitory peptides derived from food proteins: biochemistry, bioactivity and production. Curr Pharm Des. 13:773-91.
76. Murray, B. A., Walsh, D. J., and FitzGerald, R. J. (2004). Modification of the furanacryloyl-L-phenylalanylglycylglycine assay for determination of angiotensin-I-converting enzyme inhibitory activity. J. Biochem. Biophy. Methods 59:127-137.
77. Nakamura, Y., Kajimoto, O., Kaneko, K., Aihara, K., Mizutani, J., Ikeda, N., Nishimura, A. and Kajimoto, Y. (2004). Effects of the liquid yogurts containing "lactotripeptide (VPP, IPP)" on high-normal blood pressure. J. Nutr. Food. 7:123-137.
78. Nakamura, Y., Yamamoto, N., Sakai, K. and Takano, T. (1995a). Antihypertensive effect of sour milk and peptides isolated from it that are inhibitors to angiotensin I-converting enzyme. J. Dairy Sci. 78:1253-7.
79. Nakamura, Y., Yamamoto, N., Sakai, K., Okubo, A., Vamazak, S. and Takano, T. (1995b).Purification and characterization of angiotensinI-converting enzyme inhibitors from sour milk. J. Dairy Sci. 78:777-783.
80. Nurminen, M. L., Sipola, M., Kaarto, H., Pihlanto-Leppala, A., Piilola, K., Korpela, R., Tossavainen, O., Coronen, H. and Vapaatalo, H. (2000). Alpha-lactorphin lowes blood pressure measured by radiotelemetry in normotensive and spontaneously hypertensive rats. Life Sci. 66:1535-43.
81. Papadimitriou, C.G., Vafopoulou-Mastrojiannaki, A., Vieira, S., Gomes, A.-M., Xavier, F. and Alichanidis, E. (2007). Identification of peptides in traditional and probiotic sheep milk yoghurt with angiotensin I- converting enzyme (ACE) inhibitory activity. F. chemistry. 105:647-656.
82. Pihlanto-Leppälä, A. (2001). Bioactive peptides derived from bovine whey proteins: opioid and ace-inhibitory peptides. T. Food Tech. 11:347-356.
83. Pihlanto-Leppälä, A., Koskinen, P., Piilola, K., Tupasela, T. and Korhonen, H. (2000). Angiotensin I-converting enzyme inhibitory properties of whey protein digests: Concentration and characterization of active peptides. J. Dairy Res. 67:53-64.
84. Pihlanto-Leppala, A., Rokka, T. and Korhonen, H. (1998). Angiotensin I converting enzyme inhibitory peptides derived from bovine milk proteins. Int. Dairy J. 8:325-331.
85. Pins, J. J. and Keenan, J. M. (2003). The antihypertensive effects of a hydrolyzed whey protein isolate supplement (Biozate 1): A pilot study. FASEB J. 17:1110.
86. Pins, J. J. and Keenan, J. M. (2002). The antihypertensive effect of a hydrolysed whey protein isolate supplement (Biozate 1). Cardiov. Drugs Therapy. 16:S68.
87. Quirós, A., Ramos, M., Muguerza, B., Delgado, M. A., Miguel, M. and Aleixandre, A. (2007). Identification of novel antihypertensive peptides in milk fermented with Enterococus faecalis. Int. Dairy J. 17:33-41.
88. Quirós, A., Hernández-Ledesma, B., Ramos, M., Amigo, L. and Recio, I. (2005). Angiotensin-convertig enzyme inhibitory activity of peptides derived from caprine kefir. J. Dairy Sci. 88:3480-3487.
89. Riordan, J. F. (2003). Angiotensin-I-converting enzyme and its relatives. Genome Biol. 4:225.
90. Robert, P. R. and Zaloga, G. P. (1994). Dietary bioactive peptides. New Horizons. 2:237-243.
91. Roufik, S., Gauthier, S. F. and Turgeon, S. L. (2006). In vitro digestibility of bioactive peptides derived from bovine b-lactoglobulin. Int. Dairy J. 16:294-302.
92. Saito, T., Nakamura, T., Kitazawa, H., Kawai, Y. and Itoh, T. (2000). Isolation and structural analysis of antihypertensive peptides that exist naturally in gouda cheese. J. Dairy Sci. 83:1434-1440.
93. Seppo, L., Jauhiainen, T., Poussa, T. and Korpela, R. (2003). A fermented milk high in bioactive peptides has a blood pressure-lowering effect in hypertensive subjects. Am. J. Clin. Nutr. 77:326-330.
94. Seppo, L., Kerojoki, O., Suomalainen, T. and Korpela, R. (2002). The effect of a Lactobacillus helveticus LBK-16H fermented milk on hypertension: A pilot study on humans. Milchwissenschaft. 57:124-127.
95. Séverin, S. and Wenshui, X. (2005). Milk biologically active components as nutraceuticals: Review. Crit. Rev. Food Sci. Nutr. 45:645-656.
96. Sipola, M., Finckenberg, P., Santisteban, J., Korpela, R., Vapaatalo, H. and Nurminen, M.-L. (2001). Long-term intake of milk peptides attenuates de- velopment of hypertension in spontaneously hypertensive rats. J. Physiol. Pharmacol. 52:745-754.
97. Sipola, M., Finckenberg, P., Santisteban, J., Korpela, R., Vapaatalo, H. and Nurminen, M. L. (2002). Effect of long-term intake of milk products on blood pressure in hypertensive rats. J. Dairy Res. 69:103-11.
98. Steidler, L. and Rottiers, P. (2006). Therapeutic drug delivery by genetically modified Lactococcus lactis. Ann. N. Y. Acad. Sci. 1072:176-186.
99. Sugai, R. (1998). ACE inhibitors and functional foods. Bulletin of the IDF. 336:17-20.
100. Tauzin, J., Miclo, L. and Gaillard, J. L. (2002). Angiotensin-I-convertingenzyme inhibitory peptides from tryptic hydrolysate of bovine KS2-casein. FEBS Letters 531:369-374.
101. Townsend, R. R., McFadden, C. B., Ford, V. and Cadée, J. A. (2004). A randomized, double-blind, placebo-controlled trial of casein protein hydrolysaet (C12 peptide) in human essential hipertensión. Am. J. Hyperten. 17:1056-1058.
102. Tsai, J. -S., Chen, T. -J., Sun Pan, B., Gong, S. -D. and Chung, M. -Y. (2008). Antihypertensive effect of bioactive peptides produced by protease-facilitated lactic acid fermentation of milk. Food Chem. 106:552-558.
103. Tuomilehto, J., Lindstrom, J., Hyyrynen, J., Korpela, R., Karhunen, M. L. and Mikkola, L. (2004). Effect of ingesting sour milk fermented using Lactobacillus helveticus bacteria producing tripeptides on blood pressure in subjects with mild hypertension. J. Hum. Hypertens. 18:795-802.
104. Unger, T. (2002). The role of the renin-angiotensin system in the development of cardiovascular disease. Am. J. Cardiol. 89:3-9.
105. Vermeirssen, V., Van Camp, J. and Verstraete, W. (2004). Bioavailability of angiotensin I converting enzyme inhibitory peptides. Brit. J. Nutr. 92:357- 366.
106. Vermeirssen, V., Van Camp, J. and Verstraete, W. (2002). Optimization and validation of an angiotensin-converting enzyme inhibition assay for the screening of bioactive peptides. J. Biochem. Biophy. Methods 51:75-87.
107. Vermeirssen, V., Van Camp, J., Decroos, K., Van Wijmelbeke, V. and Verstraete, W. (2003). The impact of fermentation and in vitro digestion on the formation of angiotensin-I-converting enzyme inhibitory activity from pea and whey protein. J. Dairy Sci. 86:429-438.
108. Weber, M. A. (2001). Vasopeptidase inhibitors. The Lancet 358:1525-1532.
109. Witt, K. A., Sillespie, T. T., Huber, T. D. and Egleton, R. D. (2001). Peptide drug modifications to enhance bioavailability and blood-brain barrier permeability. Peptides. 22:2329-2343.
110. Yamamoto, N. and Takano, T. (1999). Antihypertensive peptides derived from milk proteins. Nahrung. 43:159-164.
111. Yamamoto, N., Akino, A. and Takano, T. (1994). Antihypertensive effect of the peptides derived from casein by an extracellular proteinase from Lactobacillus helveticus CP790. J. Dairy Sci. 77:917-922.
112. Yamamoto, N., Maeno, M. and Takano, T. (1999). Purification and characterization of an antihypertensive peptide from yoghurt-like product fermented by Lactobacillus helveticus CPN4. J. Dairy Sci. 82:1388-1393.