title: Calcium oscillations in human mesenteric vascular smooth muscle.
abstract: Phenylephrine (PE)-induced oscillatory fluctuations in intracellular Ca(2+) concentration ([Ca(2+)]i) of vascular smooth muscle have been observed in many blood vessels isolated from a wide variety of mammals. Paradoxically, until recently similar observations in humans have proven elusive. In this study, we report for the first time observations of adrenergically-stimulated [Ca(2+)]i oscillations in human mesenteric artery smooth muscle. In arterial segments preloaded with Fluo-4 AM and mounted on a myograph on the stage of a confocal microscope, we observed PE-induced oscillations in [Ca(2+)]i, which initiated and maintained vasoconstriction. These oscillations present some variability, possibly due to compromised health of the tissue. This view is corroborated by our ultrastructural analysis of the cells, in which we found only (5 ± 2)% plasma membrane-sarcoplasmic reticulum apposition, markedly less than measured in healthy tissue from laboratory animals. We also partially characterized the oscillations by using the inhibitory drugs 2-aminoethoxydiphenyl borate (2-APB), cyclopiazonic acid (CPA) and nifedipine. After PE contraction, all drugs provoked relaxation of the vessel segments, sometimes only partial, and reduced or inhibited oscillations, except CPA, which rarely caused relaxation. These preliminary results point to a potential involvement of the sarcoplasmic reticulum Ca(2+) and inositol 1,4,5-trisphosphate receptor (IP3R) in the maintenance of the Ca(2+) oscillations observed in human blood vessels.
authors: Departamento de Farmacología, Universidad Complutense, av. Séneca 2, 28040 Madrid, Spain.
authors: Jorge
authors: J
authors: Navarro-Dorado
authors: Departamento de Farmacología, Universidad Complutense, av. Séneca 2, 28040 Madrid, Spain.
authors: Mauricio
authors: M
authors: Garcia-Alonso
authors: Department of Anesthesiology, Pharmacology, and Therapeutics, The University of British Columbia, 2176 Health Sciences Mall, Medical Block C, Vancouver, BC V6T 1Z3, Canada.
authors: Cornelis
authors: C
authors: van Breemen
authors: Departamento de Farmacología, Universidad Complutense, av. Séneca 2, 28040 Madrid, Spain.
authors: Teresa
authors: T
authors: Tejerina
authors: Department of Anesthesiology, Pharmacology, and Therapeutics, The University of British Columbia, 2176 Health Sciences Mall, Medical Block C, Vancouver, BC V6T 1Z3, Canada. Electronic address: nicola.fameli@ubc.ca.
authors: Nicola
authors: N
authors: Fameli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000814:Aniline Compounds / Q000378:metabolism; D001896:Boron Compounds / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000503:physiopathology; D006973:Hypertension / Q000503:physiopathology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology* / Q000648:ultrastructure; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D009543:Nifedipine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism / Q000648:ultrastructure; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D014966:Xanthenes / Q000378:metabolism
chemical_list: D000814:Aniline Compounds; D001896:Boron Compounds; C409648:Fluo 4; D007211:Indoles; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D014966:Xanthenes; D010656:Phenylephrine; C109986:2-aminoethoxydiphenyl borate; D009543:Nifedipine; C000543:cyclopiazonic acid
keywords: 2-APB; CPA; Calcium oscillations; ER junctions; Human smooth muscle; IP(3) receptors; Mesenteric artery; Nifedipine; Sarcoplasmic reticulum