Differential calcium regulation by hydrogen peroxide and superoxide in vascular smooth muscle cells from spontaneously hypertensive rats

Journal of Cardiovascular Pharmacology
Fatiha TabetRhian M Touyz

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...Continue Reading

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Citations

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