Efectos de pravastatina en la disfunción endotelial, estrés oxidativo y otros parámetros cardiovasculares

[EN] Pravastatin, used to lower cholesterol levels, also has independent effects of lipid-lowering action. We study the effects of administration of 20 mg / kg / day of this statin for four weeks, in rats with different degrees of hypertension (spontaneously hypertensive rats, SHR). Pravastatin had no effect on systolic blood pressure in normotensive controls (WKY), prevented the rise in incipient hypertensive SHR decreased it slightly but significantly in SHR with established hypertension. Cholesterol levels were unchanged in either group. The treatment improved endothelial function of conductance arteries (aorta) and resistance (mesenteric, renal vascular bed). This effect was accompanied by an increase in the levels of NO and eNOS expression and a reduction in the expression of COX-2. In addition, the oxidative state generated cushioned by high reducing superoxide anion production stimulated by NADPH oxidase. The evaluation of morphological and histological parameters indicates that vascular remodeling caused by hypertension improved significantly after treatment. Pravastatin reduced cardiac hypertrophy, cardiomyocyte size and collagen deposition. The analysis of markers involved in fibrotic processes indicates a reduction in the expression of collagen I, fibronectin and PAI-1. Additional experiments performed quimiolumiscencia functionality and in aortic rings of SHR and Wistar indicate that the antioxidant action of pravastatin is involved, besides the inhibition of NADPH oxidase, an effect scavenger. In human arteries from patients undergoing coronary bypass surgery, incubation with pravastatin improved endothelium-dependent response and reduced the response to thromboxane and superoxide radical production. These results indicate that pravastatin, irrespective of their cholesterol-lowering effect could be beneficial in cardiovascular diseases.

Author

• Kassan, Modar

• Tesis y disertaciones académicas
• Universidad de Salamanca (España)
• Academic dissertations
• Evaluación de fármacos
• Drug Evaluation

Identifier

hdl:10366/83206

OAI identifier oai:identifier

oai:gredos.usal.es:10366/83206