Antihypertensive effects of lactoferrin hydrolyzates: Inhibition of angiotensin- and endothelin-converting enzymes

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• 作者：Ricardo Ferná ; ndez-Musoles^a ; Juan B. Salom^b ; ^c ; ^d ; Daniel Martí ; nez-Maqueda^e ; José ; Javier Ló ; pez-Dí ; ez^a ; Isidra Recio^e ; Paloma Manzanares^a ; ^{pmanz@iata.csic.es}
• 关键词：Lactoferrin hydrolyzates ; Renin&ndash ; angiotensin system ; Endothelin system ; Vasopeptidase inhibitors ; ACE-dependent vasoconstriction ; ECE-dependent vasoconstriction ; Antihypertensive effect
• 刊名：Food Chemistry
• 出版年：2013
• 出版时间：15 August, 2013
• 年：2013
• 卷：139
• 期：1-4
• 页码：994-1000
• 全文大小：451 K

文摘

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.