Antihypertensive effects of lactoferrin hydrolyzates: Inhibition of angiotensin- and endothelin-converting enzymes
The potential of bovine lactoferrin (LF) as a source of antihypertensive peptides acting on the renin-angiotensin system (RAS) and the endothelin (ET) system as dual vasopeptidase inhibitors has been examined. For this purpose enzymatic LF hydrolyzates (LFHs) were generated by trypsin and proteinase K digestions. Permeate fractions with molecular masses lower than 3 kDa (LFH <3 kDa) were orally administered to spontaneously hypertensive rats (SHRs). Although both LFHs <3 kDa showed in vitro angiotensin I-converting enzyme (ACE)-inhibitory activity, only proteinase K LFH <3 kDa exerted an in vivo antihypertensive effect. The proteinase K LFH <3 kDa and a previously characterized pepsin LFH <3 kDa with ACE-inhibitory and antihypertensive effects were tested in ex vivo functional assays as inhibitors of ACE-dependent vasoconstriction. Pepsin LFH <3 kDa but not proteinase K LFH <3 kDa inhibited ACE-dependent vasoconstriction. When tested as inhibitors towards endothelin-converting enzyme (ECE), both LFHs <3 kDa exerted in vitro inhibitory effects on ECE activity and inhibited ECE-dependent vasoconstriction. Most abundant peptides in proteinase K LFH <3 kDa were identified by using an ion trap mass spectrometer. Based on peptide abundance, two peptides (GILRPY and REPYFGY) were chemically synthesized and their ECE-inhibitory activity was tested. Both exerted in vitro inhibitory effects on ECE activity. In conclusion, orally effective antihypertensive LFHs <3 kDa may act as dual vasopeptidase (ACE/ECE) or as single ECE inhibitors with different antivasoconstrictor effects depending on the protease used to release bioactive peptide sequences. © 2013 Elsevier Ltd. All rights reserved.
| Main Authors: | , , , , , |
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| Other Authors: | |
| Format: | artículo biblioteca |
| Published: |
2013
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| Subjects: | Lactoferrin hydrolyzates, ECE-dependent vasoconstriction, ACE-dependent vasoconstriction, Renin–angiotensin system, Endothelin system, Vasopeptidase inhibitors, |
| Online Access: | http://hdl.handle.net/10261/99738 http://dx.doi.org/10.13039/501100004587 |
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