title: Role of vascular Kinin B1 and B2 receptors in endothelial nitric oxide metabolism.
abstract: Kinin B(1) and B(2) receptors play an essential role in inflammatory process and cardiovascular homeostasis. The present study investigated the vascular reactivity and nitric oxide (NO) generation in the isolated mesenteric arteriolar bed from B(1) (B(1)(-/-)) and B(2) receptor (B(2)(-/-)) knockout mice. Endothelial-dependent relaxation was significantly decreased in arterioles from both B(1)(-/-) and B(2)(-/-) in comparison to wild type (WT) mice, with no differences for endothelial-independent relaxating or vasoconstrictor agents. Plasmatic and vascular NO production were markedly reduced in both B(1)(-/-) and B(2)(-/-). In contrast, in the presence of l-arginine, Ca(2+) and co-factors for the enzyme, NO synthase activity was higher in homogenates of mesenteric vessels of B(1)(-/-) and B(2)(-/-). The present study demonstrated that targeted deletion of B(1) or B(2) receptor gene in mice induces important alterations in the vascular reactivity of resistance vessels and NO metabolism. The severe impairment in the endothelial-mediated vasodilation accompanied by decreased NO bioavailability, despite the augmented NOS activity, strongly indicates an exacerbation of NO inactivation in B(1)(-/-) and B(2)(-/-) vessels. The present data provide valuable information in order to clarify the relevance of kinin receptors in regulating vascular physiology and may point to new approaches regarding its correlation with endothelial dysfunction, oxidative stress and NO availability.
authors.affiliation: Department of Biophysics, Federal University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Loiola
authors.forename: Felipe C G
authors.initials: FC
authors.lastname: Reis
authors.forename: Elisa M
authors.initials: EM
authors.lastname: Kawamoto
authors.forename: Cristoforo
authors.initials: C
authors.lastname: Scavone
authors.forename: Dulcinéia S
authors.initials: DS
authors.lastname: Abdalla
authors.forename: Liliam
authors.initials: L
authors.lastname: Fernandes
authors.forename: João Bosco
authors.initials: JB
authors.lastname: Pesquero
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D043783:Receptor, Bradykinin B1 / Q000235:genetics / Q000378:metabolism*; D043782:Receptor, Bradykinin B2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase