Journal article
Zinc drives vasorelaxation by acting in sensory nerves, endothelium and smooth muscle
AH Betrie, JA Brock, OF Harraz, AI Bush, GW He, MT Nelson, JA Angus, CE Wright, S Ayton
Nature Communications | NATURE RESEARCH | Published : 2021
Abstract
Zinc, an abundant transition metal, serves as a signalling molecule in several biological systems. Zinc transporters are genetically associated with cardiovascular diseases but the function of zinc in vascular tone regulation is unknown. We found that elevating cytoplasmic zinc using ionophores relaxed rat and human isolated blood vessels and caused hyperpolarization of smooth muscle membrane. Furthermore, zinc ionophores lowered blood pressure in anaesthetized rats and increased blood flow without affecting heart rate. Conversely, intracellular zinc chelation induced contraction of selected vessels from rats and humans and depolarized vascular smooth muscle membrane potential. We demonstrat..
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Grants
Awarded by American Heart Association
Funding Acknowledgements
We thank the Warner Babcock Institute for Green Chemistry, Massachusetts, USA (for the supply of clioquinol and Zn(DTSM)); Nicholas Veldhuis (Monash University, Australia) for the supply of the hTRPA1- and hTRPV1-expressing HEK293 cells; Mr. Mark Ross-Smith and Ms. Linda Cornthwaite-Duncan (University of Melbourne, Australia); Ms. Irene Volitakis (Florey Institute of Neuroscience and Mental Health, Australia) and Mr. Hai-tao Hou (TEDA International Cardiovascular Hospital, China) for expert technical assistance. Supported by funds from the Australian National Health & Medical Research Council (NHMRC: APP1113686 to S.A., APP1103703 to A.I.B.). The Florey Institute of Neuroscience and Mental Health acknowledges support from the Victorian Government, in particular, funding from the Operational Infrastructure Support Grant. This study was supported by a postdoctoral fellowship (17POST33650030 to O.F.H.) and a Career Development Award (20CDA35310097 to O.F.H.) from the American Heart Association, the Totman Medical Research Trust (to M.T.N.), grants from the Fondation Leducq Transatlantic Network of Excellence on the Pathogenesis of Small Vessel Disease of the Brain (to MTN), the European Union Horizon 2020 Research and Innovation Program SVDs@target under the grant agreement n degrees 666881 (to M.T.N.), and grants from the National Institutes of Health (P20-GM-135007 to O.F.H. and M.T.N., P01-HL-095488, R01-HL-121706, R37-DK-053832, 7UM-HL-1207704 and R01-HL-131181 to M.T.N.). The research was also supported by the National Institute of Neurological Disorders and Stroke (NINDS) and National Institute of Aging (NIA) (R01NS110656) and by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number R35HL140027 to MTN. Supported also by the Tianjin Binhai New Area Science and Technology Association for James Angus Work Station at the TEDA International Cardiovascular Hospital, China to GWH. No funder of this study had any role in the design or conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the paper; or decision to submit the paper for publication.