title: Urodilatin reverses the detrimental influence of bradykinin in acute ischemic stroke.
abstract: Occlusion of cerebral arteries leads to ischemic stroke accompanied by subsequent brain edema. Bradykinin (BK) is involved in the formation of cerebral edema, and natriuretic peptides (NPs) potentially have beneficial effects on brain edema formation via a still unknown mechanism. The aim of this study was clarifying the mechanisms of action of NPs on BK signaling, and their interactive effects after ischemic brain injury. We used a mouse model for stroke, the middle cerebral artery (MCA) occlusion. Brain lesion and edema were measured by microcomputerized tomography volumetric measurements. To determine the effects of NPs on the BK signaling pathway in the MCAs we measured changes in vessel diameter and membrane potentials in endothelial cells. To determine the effects of NPs on BK signaling pathway in isolated astrocytes and neurons, membrane potentials and intercellular Ca2+concentrations were measured. Urodilatin inhibited and when applied together with BK, reduced the formation of the ischemic lesion via activation of G-Protein-Signaling Protein Type 4 at the cellular (atrocities, neurons) and blood vessel (endothelial cells and isolated MCA) level as well as in in vivo experiments. The results of this study show the existence of a natural antagonist of BK in the brain, and the possible use of NPs in the treatment of stroke.
authors.affiliation: Department of Histology and Embryology, University of Zagreb, School of Medicine, Croatia; Croatian Institute for Brain Research, University of Zagreb, School of Medicine, Croatia.
authors.forename: Marina
authors.initials: M
authors.lastname: Dobrivojević
authors.affiliation: Croatian Institute for Brain Research, University of Zagreb, School of Medicine, Croatia; Department of Anatomy, Histology and Embryology, University of Zagreb, Faculty of Veterinary Medicine, Croatia.
authors.forename: Katarina
authors.initials: K
authors.lastname: Špiranec
authors.affiliation: Department of Histology and Embryology, University of Zagreb, School of Medicine, Croatia; Croatian Institute for Brain Research, University of Zagreb, School of Medicine, Croatia.
authors.forename: Dunja
authors.initials: D
authors.lastname: Gorup
authors.affiliation: Department of Anatomy, University of Zagreb, School of Medicine, Croatia.
authors.forename: Igor
authors.initials: I
authors.lastname: Erjavec
authors.affiliation: Croatian Institute for Brain Research, University of Zagreb, School of Medicine, Croatia; Department of Physiology and Immunology, University of Zagreb, School of Medicine, Croatia.
authors.forename: Nikola
authors.initials: N
authors.lastname: Habek
authors.affiliation: Croatian Institute for Brain Research, University of Zagreb, School of Medicine, Croatia.
authors.forename: Marin
authors.initials: M
authors.lastname: Radmilović
authors.affiliation: Clinical Hospital Center Osijek, Faculty of Medicine, University of Osijek, Croatia.
authors.forename: Sanela
authors.initials: S
authors.lastname: Unfirer
authors.affiliation: Department of Physiology and Immunology, University of Osijek, Faculty of Medicine, Croatia.
authors.forename: Anita
authors.initials: A
authors.lastname: Ćosić
authors.affiliation: Clinical Hospital Center Osijek, Faculty of Medicine, University of Osijek, Croatia; Department of Physiology and Immunology, University of Osijek, Faculty of Medicine, Croatia.
authors.forename: Ines
authors.initials: I
authors.lastname: Drenjančević
authors.affiliation: Department of Histology and Embryology, University of Zagreb, School of Medicine, Croatia; Croatian Institute for Brain Research, University of Zagreb, School of Medicine, Croatia. Electronic address: srecko.gajovic@mef.hr.
authors.forename: Srećko
authors.initials: S
authors.lastname: Gajović
authors.affiliation: Croatian Institute for Brain Research, University of Zagreb, School of Medicine, Croatia; Department of Physiology and Immunology, University of Zagreb, School of Medicine, Croatia. Electronic address: aleksandra.sindic@mef.hr.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Sinđić
keywords: Atrial natriuretic peptide; Brain natriuretic peptide; C type natriuretic peptide; Urodilatin; cGMP