In:
Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 102, No. 19 ( 2000-11-07), p. 2402-2410
Abstract:
Background —Oxidized LDL reduces NO-mediated and endothelium-derived hyperpolarizing factor–mediated dilations. We studied, in hamster skeletal muscle resistance arteries (213±8 μm; n=51), whether an altered vascular smooth muscle (VSM) response, particularly sensitization of the VSM contractile apparatus to Ca 2+ , is involved in this oxLDL effect. Methods and Results —VSM or endothelial [Ca 2+ ] i and vascular diameter were measured in response to norepinephrine (0.3 μmol/L), sodium nitroprusside (10 μmol/L), C-type natriuretic peptide (1 to 100 nmol/L), papaverine (0.1 to 10 μmol/L), or the endothelial agonist acetylcholine (ACh, 0.01 to 1 μmol/L). OxLDL significantly increased resting VSM [Ca 2+ ] i (11±3%), decreased diameter (8±2%), and enhanced norepinephrine-induced constrictions. Dilations to sodium nitroprusside and C-type natriuretic peptide were significantly reduced (by 10±2% and 35±6%), whereas dose-response curves for papaverine and ACh were shifted to the right, despite unchanged increases in endothelial Ca 2+ after ACh. OxLDL significantly shifted the Ca 2+ -diameter relation to the left, as assessed by stepwise increasing extracellular Ca 2+ (0 to 3 mmol/L) in depolarized skeletal muscle resistance arteries. This sensitization to Ca 2+ by oxLDL was abolished after inhibition of Rho (C3 transferase) or Rho kinase (Y27632). Conclusions —OxLDL reduces VSM responsiveness to vasodilators by increasing VSM Ca 2+ but preferentially by sensitizing VSM to Ca 2+ via a Rho- and Rho kinase–dependent pathway.
Type of Medium:
Online Resource
ISSN:
0009-7322
,
1524-4539
DOI:
10.1161/01.CIR.102.19.2402
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2000
detail.hit.zdb_id:
1466401-X
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