Tabet, F., Savoia, C., Schiffrin, E.L. and Touyz, R.M. (2004) Differential calcium regulation by hydrogen peroxide and superoxide in vascular smooth muscle cells from spontaneously hypertensive rats. Journal of Cardiovascular Pharmacology, 44(2), pp. 200-208. (doi: 10.1097/00005344-200408000-00009)
Full text not currently available from Enlighten.
Publisher's URL: http://dx.doi.org/10.1097/00005344-200408000-00009
Abstract
We investigated the role of reactive oxygen species (ROS), particularly hydrogen peroxide (H2O2) and superoxide anion (•O2-) in the regulation of vascular smooth muscle cell (VSMC) Ca2+ concentration ([Ca2+]i) and vascular contraction and assessed whether redox-dependent Ca2+ signaling and contraction are altered in hypertension. VSMCs and mesenteric arteries from Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) were studied. Cells were stimulated with H2O2 (10-4 mol/l) or LY83583 (•O2- generator, 10-5 mol/l). [Ca2+]i and cytosolic •O2 - were measured by fura-2AM and tempo-9-AC fluorescence respectively. L-type and T-type Ca2+ channels were assessed using verapamil/diltiazem and mibefradil respectively and mRNA and protein expression of these channels was assessed by real-time PCR and immunoblotting respectively. H2O2 time-dependently increased [Ca2+]i and contraction with significantly greater effects in SHR versus WKY (P < 0.001). LY83583 increased [Ca2+]i in both strains, but responses were blunted in SHR. Removal of extracellular Ca2+ abrogated [Ca2+]i responses to H2O2 and •O2-. Verapamil and diltiazem, but not mibefradil, significantly decreased H2O2 -induced [Ca2+]i responses with greater effects in SHR (P < 0.01). L-type and T-type Ca2+ channel inhibition reduced LY83583-mediated [Ca2+]i increase only in WKY cells. Both types of Ca2+ channels were expressed (mRNA and protein) in VSMCs from WKY and SHR, with greater abundance in SHR than WKY (2- to 3-fold). These results demonstrate that ROS increase vascular [Ca2+]i and contraction, primarily via extracellular Ca2+ influx. Whereas responses to H2O2 are enhanced, •O2- -mediated actions are blunted in SHR. These effects may relate to differential activation of Ca2+ channels by H2O2 and •O2 -. Enhanced activation of L-type Ca2+ channels and increased Ca2+ influx by H2O2 may contribute to increased Ca2+ signaling in VSMCs from SHR.
Item Type: | Articles |
---|---|
Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Touyz, Professor Rhian |
Authors: | Tabet, F., Savoia, C., Schiffrin, E.L., and Touyz, R.M. |
College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
Journal Name: | Journal of Cardiovascular Pharmacology |
ISSN: | 0160-2446 |
ISSN (Online): | 1533-4023 |
University Staff: Request a correction | Enlighten Editors: Update this record