Antihypertensive properties of lactoferricin B-derived peptides.
A set of eight lactoferricin B (LfcinB)-derived peptides was examined for inhibitory effects on angiotensin I-converting enzyme (ACE) activity and ACE-dependent vasoconstriction, and their hypotensive effect in spontaneously hypertensive rats (SHR). Peptides were derived from different elongations both at the C-terminal and N-terminal ends of the representative peptide LfcinB(20-25), which is known as the LfcinB antimicrobial core. All of the eight LfcinB-derived peptides showed in vitro inhibitory effects on ACE activity with different IC(50) values. Moreover, seven of them showed ex vivo inhibitory effects on ACE-dependent vasoconstriction. No clear correlation between in vitro and ex vivo inhibitory effects was found. Only LfcinB(20-25) and one of its fragments, F1, generated after a simulated gastrointestinal digestion, showed significant antihypertensive effects in SHR after oral administration. Remarkably, F1 did not show any effect on ACE-dependent vasoconstriction in contrast to the inhibitory effect showed by LfcinB(20-25). In conclusion, two LfcinB-derived peptides lower blood pressure and exhibit potential as orally effective antihypertensive compounds, yet a complete elucidation of the mechanism(s) involved deserves further ongoing research.
Ruiz-Giménez
Pedro
P
Departamento de Biotecnología de Alimentos, Instituto de Agroquímica y Tecnología de Alimentos, Consejo Superior de Investigaciones Científicas, Burjassot, Valencia, Spain.
Ibáñez
Aida
A
Salom
Juan B
JB
Marcos
Jose F
JF
López-Díez
Jose Javier
JJ
Vallés
Salvador
S
Torregrosa
Germán
G
Alborch
Enrique
E
Manzanares
Paloma
P
D000595:Amino Acid Sequence; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry; D004195:Disease Models, Animal; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007781:Lactoferrin / Q000008:administration & dosage*; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011918:Rats, Inbred SHR
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D010455:Peptides; C082171:lactoferricin B; D007703:Peptidyl-Dipeptidase A; D007781:Lactoferrin