title: Leptin-Induced Endothelium-Independent Vasoconstriction in Thoracic Aorta and Pulmonary Artery of Spontaneously Hypertensive Rats: Role of Calcium Channels and Stores.
abstract: Decreased leptin-induced endothelium-dependent vasodilation has been reported in spontaneously hypertensive rats (SHR). Here, we report leptin-induced vasoconstriction in endothelium-denuded pulmonary artery and thoracic aorta from SHR and sought to characterize calcium handling underlying these mechanisms. Vasoreactivity to leptin was evaluated on pulmonary artery and thoracic aorta rings from 18 weeks old male SHR with or without calcium free medium, caffeine + thapsigargin + carbonyl cyanide-4-trifluoromethoxyphenylhydrazone emptying intracellular calcium stores, nifedipine a voltage-gated calcium channel inhibitor, SKF-96365 a transient receptor potential cation channels (TRPC) inhibitor, wortmaninn, a phosphatidylinositide 3-kinases (PI3K) inhibitor, or PD98059 a mitogen-activated protein kinase kinase (MAPKK) inhibitor. Calcium imaging was performed on cultured vascular smooth muscle cells incubated with leptin in presence or not of wortmaninn or PD98059. Leptin induced vasoconstriction in denuded pulmonary artery and thoracic aorta from SHR. Response was abolished when intra- or extracellular calcium stores were emptied, after blocking TRPC or voltage-dependent calcium channels or when using MAPKK or PI3K inhibitors. In vascular smooth muscle cells, leptin increased intracellular calcium. This rise was higher in SHR and abolished by MAPKK or PI3K inhibitors. TRPC6 gene expression was upregulated in arteries from SHR. Leptin-induced vasoconstriction in denuded arteries of SHR requires intracellular stores and is TRPC- and voltage-gated calcium channels dependent. Intracellular calcium increase is more pronounced in spontaneously hypertensive rats.
authors.affiliation: Laboratory of Physiology and Pharmacology, Université Libre de Bruxelles, Campus Erasme, Brussels, Belgium.
authors.forename: Samantha
authors.initials: S
authors.lastname: Gomart
authors.affiliation: Laboratory of Physiology and Pharmacology, Université Libre de Bruxelles, Campus Erasme, Brussels, Belgium.|Faculty of Medicine, University of Montréal, Montréal, Canada.
authors.forename: Caroline
authors.initials: C
authors.lastname: Gaudreau-Ménard
authors.affiliation: Laboratory of Physiology and Pharmacology, Université Libre de Bruxelles, Campus Erasme, Brussels, Belgium.
authors.forename: Pascale
authors.initials: P
authors.lastname: Jespers
authors.affiliation: Faculty of Veterinary Medicine, Department of Anatomy, University of Mehmet Akif Ersoy, Burdur, Turkey.
authors.forename: Omer Gurkan
authors.initials: OG
authors.lastname: Dilek
authors.affiliation: Laboratory of Physiology and Pharmacology, Université Libre de Bruxelles, Campus Erasme, Brussels, Belgium.
authors.forename: Emeline
authors.initials: E
authors.lastname: Hupkens
authors.affiliation: Laboratory of Physiology and Pharmacology, Université Libre de Bruxelles, Campus Erasme, Brussels, Belgium.
authors.forename: Aliénor
authors.initials: A
authors.lastname: Hanthazi
authors.affiliation: Laboratory of Physiology and Pharmacology, Université Libre de Bruxelles, Campus Erasme, Brussels, Belgium.
authors.forename: Robert
authors.initials: R
authors.lastname: Naeije
authors.affiliation: Emergency Department, Erasme University Hospital, and Biostatistics Université Libre de Bruxelles, Campus Erasme, Brussels, Belgium.
authors.forename: Christian
authors.initials: C
authors.lastname: Melot
authors.affiliation: Laboratory of Physiology and Pharmacology, Université Libre de Bruxelles, Campus La Plaine, Brussels, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Labranche
authors.affiliation: Laboratory of Physiology and Pharmacology, Université Libre de Bruxelles, Campus Erasme, Brussels, Belgium.
authors.forename: Laurence
authors.initials: L
authors.lastname: Dewachter
authors.affiliation: Laboratory of Physiology and Pharmacology, Université Libre de Bruxelles, Campus Erasme, Brussels, Belgium.
authors.forename: Kathleen
authors.identifier: http://orcid.org/0000-0003-3521-9232
authors.initials: K
authors.lastname: Mc Entee
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006973:Hypertension / Q000503:physiopathology*; D020738:Leptin / Q000008:administration & dosage / Q000378:metabolism*; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D020738:Leptin; D019869:Phosphatidylinositol 3-Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D002118:Calcium