The potential of bovine lactoferrin (LF) as a source of antihypertensive peptides has been examined. For this purpose, LF pepsin hydrolysate with molecular mass lower than 3 kDa (LFH < 3 kDa) was prepared and orally administered to spontaneously hypertensive rats (SHR), resulting in reduced systolic blood pressure in a significant and maintained manner up to 24 h after administration. LFH < 3 kDa was further fractionated by semi-preparative high performance liquid chromatography (HPLC) and 38 peptides, contained in the active fractions, were identified by using an ion trap mass spectrometer. Based on the peptide abundance, a total of 11 peptides were chemically synthesized and their ACE inhibitory activity tested. Only three of them, corresponding to peptides of sequences LIWKL, RPYL and LNNSRAP exerted in vitro inhibitory effects on angiotensin I converting enzyme (ACE) activity and had a 50% inhibitory concentration (IC50) of 0.47, 56.5 and 105.3 μM, respectively. The three peptides also showed antihypertensive effects in SHR and remarkably the effect of LIWKL remained significant for up to 24 h post-administration, similarly LFH < 3 kDa and the captopril control. The two most potent in vitro inhibitory peptides showed ex vivo inhibitory effect on ACE-dependent vasoconstriction as well. In conclusion, three novel LF-derived peptides and a pepsin LFH < 3 kDa lowered blood pressure and exhibit potential as orally effective antihypertensive compounds. © 2011 Elsevier Ltd. All rights reserved.

This work was supported by Grants AGL2007-64672/ALI and AGL2007-65035 from ‘Ministerio de Educación y Ciencia – FEDER’, Consolider Ingenio 2010, Fun-C-Food, CSD2007-00063, and RETICS- RD06/0026/0006 from ‘Instituto de Salud Carlos III’. P. Ruiz- Giménez is recipient of a fellowship from ‘Ministerio de Educación y Ciencia’ (BES-2005-10382).

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