title: Hypotensive effects of hemopressin and bradykinin in rabbits, rats and mice. A comparative study.
abstract: Hemopressin is a novel vasoactive nonapeptide derived from hemoglobin's alpha-chain as recently reported by Rioli et al. [Rioli V, Gozzo FC, Heimann AS, Linardi A, Krieger JE, Shida CS, et al. Novel natural peptide substrates for endopeptidase 24.15, neurolysin, and angiotensin-converting enzyme. J Biol Chem 2003;278(10):8547-55]. In anesthetized male Wistar rats, this peptide exhibited hypotensive actions similar to those of bradykinin (BK) when administered intravenously (i.v.), and was found to be metabolized both in vitro and in vivo by several peptidases, including the angiotensin-converting enzyme (ACE). In this study, these findings were expanded upon by examining: (i) the degradation kinetics following incubation with ACE purified from rabbit lung and (ii) the blood pressure lowering effects of HP and BK injected i.v. or intra-arterially (i.a.) in male rabbits, rats, and mice. Our findings demonstrate that, in vitro, HP and BK are both degraded by ACE, but at different velocity rates. Furthermore, both HP and BK induced transient hypotension in all animals tested, although the responses to HP relative to the administration sites were significantly lower (by 10-100-fold) on an equimolar basis compared to those of BK. In rabbits, the decrease of blood pressure induced by HP (10-100 nmol/kg) did not differ whether it was administered i.v. or i.a., suggesting an absence of pulmonary/cardiac inactivation in contrast to BK (0.1-1 nmol/kg). The in vivo effect of HP was significantly potentiated in rabbits immunostimulated with bacterial lipopolysaccharide (LPS), but was unaffected by both the B2 receptor antagonist HOE 140 (0.1 micromol/kg) and captopril (100 microg/kg), contrary to BK. Therefore, HP acts as a weak hypotensive mediator, which does not activate kinin B2 receptors, but uses a functional site and/or signaling paths appearing to be up-regulated by LPS.
authors.affiliation: Faculty of Medicine, Department of Pharmacology, Université de Sherbrooke, 301 12th North Avenue, Fleurimont, Sherbrooke, Que., Canada J1H 5N4.
authors.forename: Paul-André
authors.initials: PA
authors.lastname: Blais
authors.forename: Jérôme
authors.initials: J
authors.lastname: Côté
authors.forename: Josée
authors.initials: J
authors.lastname: Morin
authors.forename: Annie
authors.initials: A
authors.lastname: Larouche
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Gendron
authors.forename: Audrey
authors.initials: A
authors.lastname: Fortier
authors.forename: Domenico
authors.initials: D
authors.lastname: Regoli
authors.forename: Witold
authors.initials: W
authors.lastname: Neugebauer
authors.forename: Fernand
authors.initials: F
authors.lastname: Gobeil
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D001920:Bradykinin / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D006454:Hemoglobins / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity
chemical_list: D006454:Hemoglobins; D008070:Lipopolysaccharides; D010446:Peptide Fragments; C473218:hemopressin; D007703:Peptidyl-Dipeptidase A; D001920:Bradykinin