title: Brief serotonin exposure initiates arteriolar inward remodeling processes in vivo that involve transglutaminase activation and actin cytoskeleton reorganization.
abstract: Inward remodeling of the resistance vasculature is strongly associated with life-threatening cardiovascular events. Previous studies have demonstrated that both actin polymerization and the activation of transglutaminases mediate early stages of the transition from a structurally normal vessel to an inwardly remodeled one. Ex vivo studies further suggest that a few hours of exposure to vasoconstrictor agonists induces inward remodeling in the absence of changes in intraluminal pressure. Here we report that a short, 10-min, topical exposure to serotonin (5-HT) + N(ω)-nitro-l-arginine methyl ester hydrochloride (l-NAME) was sufficient to initiate inward remodeling processes in rat cremasteric feed arterioles (100-200 μm lumen diameter), in vivo. Addition of the transglutaminase inhibitor, cystamine, blocked the in vivo remodeling. We further demonstrate that, in isolated arterioles, 5-HT + l-NAME activates transglutaminases and modulates the phosphorylation state of cofilin, a regulator of actin depolymerization. The 5-HT + l-NAME-induced remodeling process in isolated arterioles was also inhibited by an inhibitor of Lim Kinase, the kinase that phosphorylates and inactivates cofilin. Therefore, our results indicate that a brief vasoconstriction induced by 5-HT + l-NAME is able to reduce the passive structural diameter of arterioles through processes that are dependent on the activation of transglutaminases and Lim kinase, and the subsequent phosphorylation of cofilin.
authors.affiliation: Dalton Cardiovascular Research Center, and Department of Medical Pharmacology and Physiology, University of Missouri-Columbia, Columbia, Missouri;
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Foote
authors.affiliation: Dalton Cardiovascular Research Center, and Department of Medical Pharmacology and Physiology, University of Missouri-Columbia, Columbia, Missouri; Department of Biological Engineering, University of Missouri-Columbia, Columbia, Missouri; and.
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Castorena-Gonzalez
authors.affiliation: Dalton Cardiovascular Research Center, and Department of Medical Pharmacology and Physiology, University of Missouri-Columbia, Columbia, Missouri;
authors.forename: Marius C
authors.initials: MC
authors.lastname: Staiculescu
authors.affiliation: College of Applied Health Sciences, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Clifford
authors.affiliation: Dalton Cardiovascular Research Center, and Department of Medical Pharmacology and Physiology, University of Missouri-Columbia, Columbia, Missouri;
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hill
authors.affiliation: Dalton Cardiovascular Research Center, and Department of Medical Pharmacology and Physiology, University of Missouri-Columbia, Columbia, Missouri;
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Meininger
authors.affiliation: Dalton Cardiovascular Research Center, and Department of Medical Pharmacology and Physiology, University of Missouri-Columbia, Columbia, Missouri; Department of Biological Engineering, University of Missouri-Columbia, Columbia, Missouri; and martinezlemusl@missouri.edu.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Martinez-Lemus
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects* / Q000378:metabolism*; D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000818:Animals; D001160:Arterioles / Q000187:drug effects*; D003538:Cystamine / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology*; D011503:Transglutaminases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D051339:Actin Depolymerizing Factors; D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D012701:Serotonin; D011503:Transglutaminases; D003538:Cystamine; D019331:NG-Nitroarginine Methyl Ester
keywords: cytoskeleton; hypertension; inward remodeling; nitric oxide; vasoconstriction; vasospasm