title: Membrane depolarization, elevated Ca(2+) entry, and gene expression in cerebral arteries of hypertensive rats.
abstract: Elevated intracellular Ca(2+) ([Ca(2+)](i)) has been implicated in contractile and phenotypic changes in arterial smooth muscle during hypertension. This study examined the role of membrane potential and [Ca(2+)](i) in altered gene expression in cerebral arteries of a rat (Dahl) genetic model of salt-sensitive hypertension. Cerebral arteries from hypertensive animals (Dahl salt-sensitive) exhibited a tonic membrane depolarization of approximately 15 mV compared with normotensive (Dahl salt-resistant) animals. Consistent with this membrane depolarization, voltage-dependent K(+) currents were decreased in cerebral artery myocytes isolated from hypertensive animals. Arterial wall Ca(2+) was elevated in cerebral arteries from hypertensive animals, an effect reversed by diltiazem, a blocker of voltage-dependent Ca(2+) channels. This depolarization-induced increase in [Ca(2+)](i) was associated with increased activation of the transcription factor, cAMP response element binding protein, and increased expression of the immediate early gene c-fos, both of which are reversed by acute exposure to the voltage-dependent Ca(2+) channel blocker nisoldipine. This study provides the first information linking altered Ca(2+) handling to changes in gene expression in cerebral arteries during hypertension.
authors.affiliation: Department of Pharmacology, The University of Vermont College of Medicine, Burlington, Vermont 05405, USA. gwellman@zoo.uvm.edu
authors.forename: G C
authors.initials: GC
authors.lastname: Wellman
authors.forename: L
authors.initials: L
authors.lastname: Cartin
authors.forename: D M
authors.initials: DM
authors.lastname: Eckman
authors.forename: A S
authors.initials: AS
authors.lastname: Stevenson
authors.forename: C M
authors.initials: CM
authors.lastname: Saundry
authors.forename: W J
authors.initials: WJ
authors.lastname: Lederer
authors.forename: M T
authors.initials: MT
authors.lastname: Nelson
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D002536:Cerebral Arteries / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology*; D008564:Membrane Potentials / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D015737:Nisoldipine / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D051381:Rats; D020303:Rats, Inbred Dahl
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D017362:Cyclic AMP Response Element-Binding Protein; D024642:Potassium Channels, Voltage-Gated; D016760:Proto-Oncogene Proteins c-fos; D015737:Nisoldipine; D002118:Calcium