title: Antihypertensive mechanism of lactoferrin-derived peptides: angiotensin receptor blocking effect.
abstract: Looking for antihypertensive mechanisms beyond ACE inhibition, we assessed whether lactoferrin (LF)-derived peptides can act as receptor blockers to inhibit vasoconstriction induced by angiotensin II or endothelin-1. The lactoferricin B (LfcinB)-derived peptide LfcinB20-25 (RRWQWR), the low molecular weight LF hydrolysate (LFH < 3 kDa), and two peptides identified in LFH < 3 kDa (LIWKL and RPYL) were tested in ex vivo assays of vasoactive responses. The peptide RPYL was tested in radioligand receptor binding assays. Both LFH < 3 kDa and individual peptides inhibited angiotensin II-induced vasoconstriction. RPYL showed the highest ex vivo inhibitory effect and also inhibited binding of [(125)I]-(Sar(1),Ile(8))-angiotensin II to AT1 receptors. By contrast, neither LFH < 3 kDa nor RPYL inhibited endothelin-1 and depolarization-induced vasoconstrictions. In conclusion, LF-derived peptides selectively inhibit angiotensin II-induced vasoconstriction by blocking angiotensin AT1 receptors. Therefore, inhibition of angiotensin II-induced vasocontriction is suggested as a mechanism contributing along with ACE inhibition to the antihypertensive effect of some LF-derived peptides.
authors.affiliation: Departamento de Biotecnologı́a de Alimentos, Instituto de Agroquı́mica y Tecnologı́a de Alimentos, Consejo Superior de Investigaciones Científicas , Avenida Agustín Escardino 7, 46980 Paterna, Valencia, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Fernández-Musoles
authors.forename: María
authors.initials: M
authors.lastname: Castelló-Ruiz
authors.forename: Cristina
authors.initials: C
authors.lastname: Arce
authors.forename: Paloma
authors.initials: P
authors.lastname: Manzanares
authors.forename: M Dolores
authors.initials: MD
authors.lastname: Ivorra
authors.forename: Juan B
authors.initials: JB
authors.lastname: Salom
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007781:Lactoferrin / Q000737:chemistry*; D008297:Male; D008970:Molecular Weight; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry; D011817:Rabbits; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D010455:Peptides; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D007781:Lactoferrin
keywords: angiotensin receptor blocker; angiotensin-converting enzyme inhibition; antihypertensive mechanism; bovine lactoferrin hydrolysate; lactoferrin-derived peptides; renin−angiotensin system