Linked Life Data

17102939

Source:http://linkedlifedata.com/resource/pubmed/id/17102939

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-11-24
pubmed:abstractText
Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, so called statins, improve endothelial function and exert antiproliferative effects on vascular smooth muscle cells of systemic vessels. This study aimed at comparing the protective effects of two statins, pravastatin and atorvastatin, against monocrotaline (MC)-induced pulmonary hypertension in rats. Pravastatin or atorvastatin (PS or AS, 10 mg/kg per day) or vehicle were given orally for 28 days to Wistar male rats injected or not with MC (60 mg/kg intraperitoneally). At 4 weeks, MC-injected rats developed severe pulmonary hypertension, with an increase in right ventricular pressure (RVP) and right ventricle/left ventricle + septum weight ratio associated with a decrease in acetylcholine- or sodium-nitroprusside-induced pulmonary artery dilation observed in vitro. Hypertensive pulmonary arteries exhibited an increase in medial thickness and endothelial cell apoptosis and a decrease of endothelial nitric oxide synthase (eNOS) expression. MC-rat lungs showed a significant decrease of eNOS (P < 0.01) and increase of cleaved caspase-3 (P < 0.05) expression determined by Western blotting. PS (P = 0.02) but not AS (P = 0.30) significantly limited the development of pulmonary hypertension (RVP in mmHg: 30 +/- 3, 36 +/- 4 vs. 45 +/- 4 and 14 +/- 1 for MC + PS, MC + AS, MC, and control groups, respectively). Both statins significantly reduced MC-induced right ventricle hypertrophy [RV/left ventricular (LV) + S, in mg/g: 0.46 +/- 0.04, 0.39 +/- 0.03, 0.62 +/- 0.05 and 0.29 +/- 0.01 for MC + PS, MC + AS, MC, and control groups, respectively; P < 0.05),and reduced MC-induced thickening (61 +/- 6 microm, 82 +/- 5 microm, 154 +/- 4 microm, and 59 +/- 2 microm for MC + PS, MC + AS, MC, and control groups, respectively; P = 0.01) of small intrapulmonary artery medial wall, with MC + AS still being different from the control group. PS but not AS partially restored acetylcholine-induced pulmonary artery vasodilation in MC rats (E(max)=65 +/- 5%, 49 +/- 6%, 46 +/- 3%, and 76 +/- 4% for MC + PS, MC + AS, MC, and control groups, respectively; P < 0.05 for MC + PS vs. other groups). Both statins prevented apoptosis and restored eNOS expression of pulmonary artery endothelial cells as well as in the whole lung with a more pronounced effect with PS compared with AS. In conclusion, despite its effects on eNOS expression, apoptosis, and medial wall thickening, AS was unable to significantly reduce pulmonary hypertension and to restore endothelium-dependent relaxation, suggesting intermolecular differences between the two HMG-CoA reductase inhibitors in the protection against MC-induced hypertension.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0028-1298
pubmed:author
pubmed:issnType
Print
pubmed:volume
374
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
195-206
pubmed:meshHeading
pubmed-meshheading:17102939-Acetylcholine, pubmed-meshheading:17102939-Animals, pubmed-meshheading:17102939-Apoptosis, pubmed-meshheading:17102939-Caspase 3, pubmed-meshheading:17102939-Endothelial Cells, pubmed-meshheading:17102939-Heptanoic Acids, pubmed-meshheading:17102939-Hydroxymethylglutaryl-CoA Reductase Inhibitors, pubmed-meshheading:17102939-Hypertension, Pulmonary, pubmed-meshheading:17102939-Lung, pubmed-meshheading:17102939-Male, pubmed-meshheading:17102939-Monocrotaline, pubmed-meshheading:17102939-Nitric Oxide Synthase Type III, pubmed-meshheading:17102939-Nitroprusside, pubmed-meshheading:17102939-Pravastatin, pubmed-meshheading:17102939-Pulmonary Artery, pubmed-meshheading:17102939-Pyrroles, pubmed-meshheading:17102939-Rats, pubmed-meshheading:17102939-Rats, Wistar, pubmed-meshheading:17102939-Ventricular Pressure
pubmed:year
2006
pubmed:articleTitle
The protective effect of HMG-CoA reductase inhibitors against monocrotaline-induced pulmonary hypertension in the rat might not be a class effect: comparison of pravastatin and atorvastatin.
pubmed:affiliation
Laboratory of Experimental Cardiovascular Physiopathology and Pharmacology (EA2979), University of Burgundy, BP 87900, 21000, Dijon, France.
pubmed:publicationType
Journal Article, Comparative Study