The HMG-CoA reductase inhibitor, pravastatin, prevents the development of monocrotaline-induced pulmonary hypertension in the rat through reduction of endothelial cell apoptosis and overexpression of eNOS
Autor: | Zo Rakotoniaina, Luc Rochette, Marc Bardou, Frédéric Lirussi, Françoise Goirand, Monique Dumas, Pascal Guerard |
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Rok vydání: | 2006 |
Předmět: |
Male
Vascular smooth muscle Survival Vasodilator Agents Vasodilation Apoptosis Blood Pressure Poisons Enos Heart Rate Lung Pravastatin Monocrotaline biology Caspase 3 General Medicine Immunohistochemistry medicine.anatomical_structure Heart Function Tests Disease Progression Sodium nitroprusside medicine.drug Nitroprusside medicine.medical_specialty Nitric Oxide Synthase Type III Hypertension Pulmonary Blotting Western Pulmonary Artery medicine.artery Internal medicine medicine In Situ Nick-End Labeling Animals Rats Wistar Pharmacology Hypertrophy Right Ventricular business.industry Body Weight Endothelial Cells biology.organism_classification medicine.disease Pulmonary hypertension Acetylcholine Rats Endocrinology Pulmonary artery Hydroxymethylglutaryl-CoA Reductase Inhibitors business |
Zdroj: | Naunyn-Schmiedeberg's archives of pharmacology. 373(6) |
ISSN: | 0028-1298 |
Popis: | HMG-CoA reductase inhibitors improve endothelial function and exert antiproliferative effects on vascular smooth muscle cells of systemic vessels. This study was aimed to assess the protective effects of pravastatin (an HMG-CoA reductase inhibitor) against monocrotaline-induced pulmonary hypertension in rats. Pravastatin (PS, 10 mg/kg/day) or vehicle were given orally for 28 days to Wistar male rats injected or not with monocrotaline (MC, 60 mg/kg intraperitonealy) and treated or not by N(omega)-nitro-L-arginine methyl ester (L-NAME) 15 mg/kg/day. At 4 weeks, monocrotaline-injected rats developed severe pulmonary hypertension, with an increase in right ventricular pressure (RVP) and right ventricle/left ventricle+septum weight ratio (RV/LV+S), associated with a decrease in pulmonary artery dilation induced either by acetylcholine or sodium nitroprusside. Hypertensive pulmonary arteries exhibited an increase in medial thickness, medial wall area, endothelial cell apoptosis, and a decrease of endothelial nitric oxide synthase (eNOS) expression. Monocrotaline-rat lungs showed a significant decrease of eNOS expression (4080+/-27 vs 12189+/-761 arbitrary density units [ADU] for MC and control groups respectively, P |
Databáze: | OpenAIRE |
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