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Abstract
Among their pleiotropic effects, statins exert antioxidant and anti-inflammatory properties. The aim of this study was to evaluate in normotensive (WKY) and in spontaneously hypertensive rats (SHR) the effect of rosuvastatin (ROSU) treatment on (1) plasma inflammation markers and endogenous NO synthase inhibitor (ADMA) levels, (2) reactive oxygen species (ROS) generated by circulating leukocytes and (3) vascular oxidative stress and tissue inflammation markers. Plasma cytokines were higher in SHR than in WKY, except for IL-4, which was lower in SHR than in WKY. SHR monocytes exhibited higher production of ROS than did WKY monocytes. In the experimental conditions, ROSU did not modify plasma cholesterol levels in SHR but attenuated the increase in systolic blood pressure. In SHR only, ROSU lessened pro-inflammatory cytokines and ADMA levels, increased IL-4 and reduced ROS production in circulating monocytes. These results demonstrate the beneficial effects of ROSU in SHR, independently of any lowering of cholesterol levels.
| Abbreviations | ||
| ADMA | = | asymmetrical dimethyl-arginine |
| DAF-FM | = | 4-amino-5-methylamino-2′,7′-difluorofluorescein diacetate |
| DAPI | = | 4′,6-diamidino-2-phenyindole |
| DHE | = | dihydroethidium |
| EPA | = | endogenous peroxidase activity |
| GM-CSF | = | granulocyte macrophage colony-stimulating factor |
| HDL | = | high-density lipoprotein |
| HPLC | = | high performance liquid chromatography |
| HR | = | heart rate |
| IFN-γ | = | interferon-γ |
| IL | = | interleukin |
| iNOS | = | inductible NO synthase |
| LDL | = | low-density lipoprotein |
| MCP-1 | = | monocyte chemoattractant protein-1 |
| NAD(P)H | = | Nicotinamine Adenine Dinucleotide Phosphate |
| NO | = | nitric oxide |
| O2•− | = | superoxide anion |
| PBS | = | phosphate-buffered saline |
| PMNs | = | polymorphonuclear cells |
| RLU | = | relative light units |
| ROS | = | reactive oxygen species |
| ROSU | = | rosuvastatin |
| SBP | = | systolic arterial pressure |
| SDMA | = | symmetric stereoisomer dimethyl-arginine |
| SHR | = | spontaneously hypertensive rats |
| WKY | = | Wistar Kyoto. |
| Abbreviations | ||
| ADMA | = | asymmetrical dimethyl-arginine |
| DAF-FM | = | 4-amino-5-methylamino-2′,7′-difluorofluorescein diacetate |
| DAPI | = | 4′,6-diamidino-2-phenyindole |
| DHE | = | dihydroethidium |
| EPA | = | endogenous peroxidase activity |
| GM-CSF | = | granulocyte macrophage colony-stimulating factor |
| HDL | = | high-density lipoprotein |
| HPLC | = | high performance liquid chromatography |
| HR | = | heart rate |
| IFN-γ | = | interferon-γ |
| IL | = | interleukin |
| iNOS | = | inductible NO synthase |
| LDL | = | low-density lipoprotein |
| MCP-1 | = | monocyte chemoattractant protein-1 |
| NAD(P)H | = | Nicotinamine Adenine Dinucleotide Phosphate |
| NO | = | nitric oxide |
| O2•− | = | superoxide anion |
| PBS | = | phosphate-buffered saline |
| PMNs | = | polymorphonuclear cells |
| RLU | = | relative light units |
| ROS | = | reactive oxygen species |
| ROSU | = | rosuvastatin |
| SBP | = | systolic arterial pressure |
| SDMA | = | symmetric stereoisomer dimethyl-arginine |
| SHR | = | spontaneously hypertensive rats |
| WKY | = | Wistar Kyoto. |