Membrane depolarization, elevated Ca(2+) entry, and gene expression in cerebral arteries of hypertensive rats

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 sal...

Full description

Saved in:
Bibliographic Details
Published in:American journal of physiology. Heart and circulatory physiology 2001-12, Vol.281 (6), p.H2559-H2567
Main Authors: Wellman, G C, Cartin, L, Eckman, D M, Stevenson, A S, Saundry, C M, Lederer, W J, Nelson, M T
Format: Article
Language:English
Subjects:
Animals
Calcium - metabolism
Calcium Channel Blockers - pharmacology
Calcium Channels - metabolism
Cerebral Arteries - metabolism
Cyclic AMP Response Element-Binding Protein - metabolism
Gene Expression - physiology
Hypertension - metabolism
Hypertension - physiopathology
Membrane Potentials - physiology
Muscle, Smooth, Vascular - physiology
Nisoldipine - pharmacology
Potassium Channels, Voltage-Gated - metabolism
Proto-Oncogene Proteins c-fos - genetics
Rats
Rats, Inbred Dahl
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0363-6135
DOI:10.1152/ajpheart.2001.281.6.h2559