Antihypertensive Mechanism of Lactoferrin-Derived Peptides: Angiotensin Receptor Blocking Effect

Autores de IIS La Fe

• Ricardo Fernandez Musoles

  Autor

• María Castelló Ruiz

  Autor

• Paloma Manzanares Mir

  Autor

• Juan Bautista Salom Sanvalero

  Autor

Participantes ajenos a IIS La Fe

• Arce C
• Ivorra MD

Grupos

• Unidad Mixta de Investigación Cerebrovascular

  Leader

  Juan Bautista Salom Sanvalero

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 LfcinB(20-25). (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 [I-125]-(Sar(1),Ile(8))-angiotensin II to AT, 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 AT(1) 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.

Keywords

• bovine lactoferrin hydrolysate; lactoferrin-derived peptides; antihypertensive mechanism; renin angiotensin system; angiotensin-converting enzyme inhibition; arigiotensin receptor blocker