Gc. Wellman et al., Membrane depolarization, elevated Ca2+ entry, and gene expression in cerebral arteries of hypertensive rats, AM J P-HEAR, 281(6), 2001, pp. H2559-H2567
Citations number
30
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Elevated intracellular Ca2+ ([Ca2+](i)) has been implicated in contractile
and phenotypic changes in arterial smooth muscle during hypertension. This
study examined the role of membrane potential and [Ca2+](i) in altered gene
expression in cerebral arteries of a rat (Dahl) genetic model of salt-sens
itive hypertension. Cerebral arteries from hypertensive animals (Dahl salt-
sensitive) exhibited a tonic membrane depolarization of similar to 15 mV co
mpared with normotensive (Dahl salt-resistant) animals. Consistent with thi
s membrane depolarization, voltage-dependent K+ currents were decreased in
cerebral artery myocytes isolated from hypertensive animals. Arterial wall
Ca2+ was elevated in cerebral arteries from hypertensive animals, an effect
reversed by diltiazem, a blocker of voltage-dependent Ca2+ channels. This
depolarization-induced increase in [Ca2+](i) was associated with increased
activation of the transcription factor, cAMP response element binding prote
in, and increased expression of the immediate early gene c-fos, both of whi
ch are reversed by acute exposure to the voltage-dependent Ca2+ channel blo
cker nisoldipine. This study provides the first information linking altered
Ca2+ handling to changes in gene expression in cerebral arteries during hy
pertension.