Journal of Dairy Science
Volume 89, Issue 9 , Pages 3326-3335 , September 2006

Identification and Characterization of Novel Angiotensin-Converting Enzyme Inhibitors Obtained from Goat Milk

  • A. Geerlings

      Affiliations

    • Department of Biomedicine, Puleva Biotech, Camino de Purchil 66, 18004 Granada, Spain
    • A. Geerlings and I. C. Villar contributed equally to this work.
    • Corresponding Author InformationCorresponding author.
  • ,
  • I.C. Villar

      Affiliations

    • Department of Pharmacology, School of Pharmacy, University of Granada, Granada, Spain
    • A. Geerlings and I. C. Villar contributed equally to this work.
  • ,
  • F. Hidalgo Zarco

      Affiliations

    • Department of Biomedicine, Puleva Biotech, Camino de Purchil 66, 18004 Granada, Spain
  • ,
  • M. Sánchez

      Affiliations

    • Department of Pharmacology, School of Pharmacy, University of Granada, Granada, Spain
  • ,
  • R. Vera

      Affiliations

    • Department of Pharmacology, School of Pharmacy, University of Granada, Granada, Spain
  • ,
  • A. Zafra Gomez

      Affiliations

    • Department of Biomedicine, Puleva Biotech, Camino de Purchil 66, 18004 Granada, Spain
  • ,
  • J. Boza

      Affiliations

    • Department of Biomedicine, Puleva Biotech, Camino de Purchil 66, 18004 Granada, Spain
  • ,
  • J. Duarte

      Affiliations

    • Department of Pharmacology, School of Pharmacy, University of Granada, Granada, Spain

Received 5 December 2005 ,Accepted 11 April 2006.

References 

  1. 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
  2. Aihara K, Kajimoto O, Hirata H, Takahashi R, Nakamura Y. Effect of powdered fermented milk with Lactobacillus helveticus on subjects with high-normal blood pressure or mild hypertension. J. Am. Coll. Nutr. 2005;24:257–265
  3. Ariyoshi Y. Angiotensin-converting enzyme inhibitors derived from food proteins. Trends Food Sci. Technol. 1993;4:139–144
  4. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 1976;72:248–254
  5. Brown NJ, Vaughan DE. Angiotensin-converting enzyme inhibitors. Circulation. 1998;97:1411–1420
  6. Campbell DJ, Duncan AM, Kladis A, Harrap SB. Angiotensin peptides in spontaneously hypertensive and normotensive Donryu rats. Hypertension. 1995;25:928–934
  7. Chen S, Su J, Wu K, Hu W, Gardner DG, Chen D. Early captopril treatment prevents hypertrophy-dependent gene expression in hearts of SHR. Am. J. Physiol. 1998;274:R1511–R1517
  8. Duarte J, Perez-Palencia R, Vargas F, Ocete MA, Perez-Viz-caino F, Zarzuelo A, et al. Antihypertensive effects of the flavonoid quercetin in spontaneously hypertensive rats. Br. J. Pharmacol. 2001;133:117–124
  9. Dworkin LD, Grosser M, Feiner HD, Ullian M, Parker M. Renal vascular effects of antihypertensive therapy in unin-ephrectomized SHR. Kidney Int. 1989;35:790–798
  10. FitzGerald RJ, Murray BA, Walsh DJ. Hypotensive peptides from milk proteins. J. Nutr. 2004;134:980S–988S
  11. Frohlich ED, Apstein C, Chobanian AV, Devereux RB, Dustan HP, Dzau V, et al. The heart in hypertension. N. Engl. J. Med. 1992;327:998–1008
  12. Fujita H, Yoshikawa M. LKPNM: A prodrug-type ACE-inhibitory peptide derived from fish protein. Immunopharmacology. 1999;44:123–127
  13. Hata Y, Yamamoto M, Ohni M, Nakajima K, Nakamura Y, Takano T. A placebo-controlled study of the effect of sour milk on blood pressure in hypertensive subjects. Am. J. Clin. Nutr. 1996;64:767–771
  14. Lee RM, Berecek KH, Tsoporis J, McKenzie R, Triggle CR. Prevention of hypertension and vascular changes by captopril treatment. Hypertension. 1991;17:141–150
  15. Lynch JM, Barbano DM, Fleming JR. Indirect and direct determination of the casein content of milk by Kjeldahl nitrogen analysis: Collaborative study. J. AOAC Int. 1998;81:763–774
  16. Maeno M, Yamamoto N, Takano T. Identification of an antihypertensive peptide from casein hydrolysate produced by a proteinase from Lactobacillus helveticus CP790. J. Dairy Sci. 1996;79:1316–1321
  17. Meisel H. Biochemical properties of peptides encrypted in bovine milk proteins. Curr. Med. Chem. 2005;12:1905–1919
  18. Miguel M, Muguerza B, Sanchez E, Delgado MA, Recio I, Ramos M, et al. Changes in arterial blood pressure in hypertensive rats caused by long-term intake of milk fermented by Enterococcus faecalis CECT 5728. Br. J. Nutr. 2005;94:36–43
  19. Mizuno S, Matsuura K, Gotou T, Nishimura S, Kajimoto O, Yabune M, et al. 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
  20. Mullally MM, Meisel H, FitzGerald RJ. Synthetic peptides corresponding to alpha-lactalbumin and beta-lactoglobulin sequences with angiotensin-I-converting enzyme inhibitory activity. Biol. Chem. Hoppe Seyler. 1996;377:259–260
  21. Mullally MM, Meisel H, FitzGerald RJ. Identification of a novel angiotensin-I-converting enzyme inhibitory peptide corresponding to a tryptic fragment of bovine beta-lactoglobulin. FEBS Lett. 1997;402:99–101
  22. Murakami M, Tonouchi H, Takahashi R, Kitazawa H, Kawai Y, Negishi H, et al. Structural analysis of a new anti-hypertensive peptide (beta-lactosin B) isolated from a commercial whey product. J. Dairy Sci. 2004;87:1967–1974
  23. Nakamura Y, Yamamoto N, Sakai K, Okubo A, Yamazaki S, Takano T. Purification and characterization of angiotensin I-converting enzyme inhibitors from sour milk. J. Dairy Sci. 1995;78:777–783
  24. Nakamura Y, Yamamoto N, Sakai K, Takano T. Anti-hypertensive effect of sour milk and peptides isolated from it that are inhibitors to angiotensin I-converting enzyme. J. Dairy Sci. 1995;78:1253–1257
  25. National Research Council. Nutrient Requirements of Laboratory Animals. 4th rev. ed.. Washington, DC: Natl. Acad. Press; 1995;
  26. Onaka U, Fujii K, Abe I, Fujishima M. Antihypertensive treatment improves endothelium-dependent hyperpolarization in the mesenteric artery of spontaneously hypertensive rats. Circulation. 1998;98:175–182
  27. Parmley WW. Evolution of angiotensin-converting enzyme inhibition in hypertension, heart failure, and vascular protection. Am. J. Med. 1998;105:27S–31S
  28. Pihlanto-Leppala 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
  29. Rodrigo E, Maeso R, Munoz-Garcia R, Navarro-Cid J, Ruilope LM, Cachofeiro V, et al. Endothelial dysfunction in spontaneously hypertensive rats: Consequences of chronic treatment with losartan or captopril. J. Hypertens. 1997;15:613–618
  30. Schachinger V, Britten MB, Zeiher AM. Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation. 2000;101:1899–1906
  31. Seppo L, Jauhiainen T, Poussa T, Korpela R. A fermented milk high in bioactive peptides has a blood pressure-lowering effect in hypertensive subjects. Am. J. Clin. Nutr. 2003;77:326–330
  32. Sipola M, Finckenberg P, Korpela R, Vapaatalo H, Nurminen ML. Effect of long-term intake of milk products on blood pressure in hypertensive rats. J. Dairy Res. 2002;69:103–111
  33. Sipola M, Finckenberg P, Santisteban J, Korpela R, Vapaatalo H, Nurminen ML. Long-term intake of milk peptides attenuates development of hypertension in spontaneously hypertensive rats. J. Physiol. Pharmacol. 2001;52:745–754
  34. Takai S, Jin D, Sakaguchi M, Miyazaki M. Significant target organs for hypertension and cardiac hypertrophy by angiotensin-converting enzyme inhibitors. Hypertens. Res. 2004;27:213–219
  35. Tuomilehto J, Lindstrom J, Hyyrynen J, Korpela R, Karhunen ML, Mikkola L, et al. Effect of ingesting sour milk fermented using Lactobacillus helveticus bacteria producing tripeptides on blood pressure in subjects with mild hypertension. J. Hum. Hypertens. 2004;18:795–802
  36. Vanhoutte PM. Endothelial dysfunction in hypertension. J. Hypertens. 1996;14:S83–S93
  37. Wu J, Aluko RE, Muir AD. Improved method for direct high-performance liquid chromatography assay of angiotensin-converting enzyme-catalyzed reactions. J. Chromatogr. 2002;950:125–130
  38. Yang D, Feletou M, Levens N, Zhang JN, Vanhoutte PM. A diffusible substance(s) mediates endothelium-dependent contractions in the aorta of SHR. Hypertension. 2003;41:143–148

PII: S0022-0302(06)72369-4

doi: 10.3168/jds.S0022-0302(06)72369-4

Journal of Dairy Science
Volume 89, Issue 9 , Pages 3326-3335 , September 2006