Effects of chronic treatment with simvastatin on endothelial dysfunction in spontaneously hypertensive rats
作者:
María de Sotomayor,
Concepción Pérez-Guerrero,
Maria Herrera,
Elisa Marhuenda,
期刊:
Journal of Hypertension
(OVID Available online 1999)
卷期:
Volume 17,
issue 6
页码: 769-776
ISSN:0263-6352
年代: 1999
出版商: OVID
关键词: endothelium;3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors;rat isolated aorta;SHR;simvastatin
数据来源: OVID
摘要:
ObjectiveTo investigate the effects of chronic treatment with simvastatin (SV) on endothelium-dependent relaxation and ouabain-induced contractions in aortic rings from spontaneously hypertensive rats (SHR), comparing with normotensive Wistar–Kyoto rats (WKY).MethodsAfter a 12-week period of administration of 1 or 2 mg/kg SV to SHR and WKY, systolic blood pressure (SBP) and vascular reactivity in endothelium-intact aortic rings were assessed.ResultsRelaxation in response to acetylcholine (ACh) in WKY remained unaltered, but in SHR treated with 1 mg/kg SV, enhanced ACh-induced relaxation (P< 0.05 versus untreated SHR) reached values observed in untreated WKY. The 2 mg/kg treatment also improved ACh relaxation (P< 0.01 andP< 0.05 versus untreated SHR and WKY respectively). Inhibiting cyclo-oxygenase (COX) with indomethacin (INDO) improved ACh relaxation in SHR (P< 0.05) but not in WKY, independent of treatment with SV. Inhibition of nitric oxide synthase (NOS) withNG-nitro-L-arginine (L-NOARG) abolished ACh relaxations in all cases (P< 0.001). The result was unaltered when combining INDO plus L-NOARG. SV treatment also decreased ouabain-induced contractions in endotheliumintact aortic rings from SHR, diminishing the percentage effect of contraction from 64.56 ± 2.95 (untreated SHR) to 26.98 ± 7.06 and 38.10 ± 8.21 (1 and 2 mg/kg treated SHR respectively). Response to ouabain in WKY was not significantly affected by SV treatment.ConclusionsChronic treatment of SHR with SV improves endothelium-dependent ACh relaxation of the aortic rings, probably by an NO-involving mechanism more than by inhibiting contractile COX-derived factors. An improvement in endothelial modulation of ouabain-induced contractions was also observed after treatment with SV in SHR, which might be due to an inhibition of a calcium–sodium exchanger.
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