Papel de la aldosterona en las alteraciones vasculares funcionales y en el proceso inflamatorio asociados a la hipertensión en ratas / Role of aldosterone in vascular functional alterations and the inflammatory process associated to hypertension in rats

Objetivos: Estudiar la participación de la aldosterona en la disfunción vascular, el proceso inflamatorio y estrés oxidativo vascular asociado a hipertensión. Material y método: Se utilizaron ratas (n = 16) espontáneamente hipertensas (SHR) de 22 semanas de edad. La mitad de las ratas fueron tratadas durante 10 semanas con eplerenona a una dosis de 30 mg/kg/día (E-30). Se utilizaron ratas (n = 8) normotensas (WKY) como grupo de referencia. La presión arterial se midió de manera indirecta en la arteria caudal de la cola de las ratas. Al final del tratamiento las ratas se sacrificaron y se pesaron los corazones. Se evaluó la función endotelial en anillos aórticos en respuesta a la acetilcolina. La expresión del ARN mensajero (ARNm) de las interleucinas 1 β y 6 (IL-1β e IL-6), del factor de necrosis tumoral α (TNF-α), de la enzima óxido nítrico endotelial (eNOS) y de la subunidad p22phox de la enzima NAD(P)H oxidasa se midió en la aorta de las ratas. Resultados: Las SHR presentaron unos valores de presión arterial sistólica mayores (p < 0,05) que las ratas controles WKY (199,8±4,2 frente a 125,3±2,0 mmHg). El tratamiento con eplerenona redujo (p < 0,05) ligeramente las cifras de presión arterial en las ratas hipertensas (E30; 181,0±2,0 mmHg). No hubo diferencias en el peso corporal de las ratas, sin embargo el peso relativo del corazón de las ratas hipertensas era significativamente mayor respecto a las ratas normotensas y se normalizó con el tratamiento con eplerenona. La relajación a acetilcolina estaba significativamente reducida en las ratas SHR así como la expresión vascular de la eNOS. Sin embargo, las ratas hipertensas presentaron una sobreexpresión vascular del ARNm de IL-1β, IL-6, TNF-α y p22phox respecto a las WKY (p < 0,05). El tratamiento con eplerenona normalizó la función endotelial en las ratas hipertensas; aumento la expresión del ARNm de eNOS y redujo la expresión vascular de las citocinas IL-1β, IL-6, TNF-α, así como de la p22phox. Conclusiones: La aldosterona participa en las alteraciones funcionales vasculares en las SHR reduciendo la biodisponibilidad de óxido nítrico, aumentando el estrés oxidativo y el proceso inflamatorio vascular(AU)

Objetives: To study the participation of aldosterone in the vascular dysfunction, inflammatory process and vascular oxidative stress associated to hypertension. Material and methods: Half of the group of 22 week-old spontaneously hypertensive rats (n=16) were treated with eplerenone (E-30; 30 mg/kg/day) for 10 weeks. Normotensive rats (WKY; n = 8) were used as reference group. Systolic arterial pressure (SAP) was measured by the tail-cuff method. Body weight and heart weight were measured at the end of the treatment. Endothelium-dependent relaxations, as well as vascular mRNA expression of interleukin 1 β and 6 (IL-1β and IL-6), tumor necrosis factor alpha (TNF-α), of endothelial nitric oxide synthase (eNOS), NAD(P)H oxidase subunit p22phox were studied in aorta from SHR untreated or treated with eplerenone. Results: SHR showed higher levels of systolic blood pressure (p < 0.05) as compare with control rats (199.8±4.2 vs. 125.33±2.0 mmHg). Although there were no differences in the body weight among the groups, hypertensive rats had a higher relative heart weight compare to normotensive rats and it was normalize with the treatment of eplerenone (p < 0.05). SHR showed higher vascular mRNA expression of IL-1β, IL-6, TNF-α and p22phox compared to WKY (p < 0.05). Treatment with eplerenone slightly reduced (p < 0.05) blood pressure in hypertensive rats (E30; 181.0±2.0 mmHg) and normalized acetylcholine relaxations. Eplerenone enhanced (p < 0.05) eNOS and reduced p22phox, IL-1β, IL-6, TNF-α of aortic mRNA expressions in SHR. Conclusions: In SHR, aldosterone participates in the functional vascular alterations through the diminution of nitric oxide availability and the enhancement of the inflammatory process and the increase of vascular oxidative stress(AU)

Eicosanoid production, thrombogenic ratio, and serum and LDL peroxides in normo- and hypercholesterolaemic post-menopausal women consuming two oleic acid-rich diets with different content of minor components.

The present paper compares the effects of two monounsaturated oils, extra virgin olive oil (EVOO) and high-oleic acid sunflower oil (HOSO), on serum and LDL peroxides, eicosanoid production and the thrombogenic ratio (thromboxane (TX) B2:6-keto-prostaglandin F1alpha) in fourteen non-obese post-menopausal women. The subjects, mean age 63 (SD 11) years, were assigned to two consecutive oleic acid-rich 28 d dietary periods. EVOO and HOSO represented 62 % of the total lipid intake and were used as the only culinary fat during the first and second dietary periods respectively. Serum peroxides, plasma alpha-tocopherol and TXB2 levels in stimulated platelet-rich plasma (PRP-TXB2) were significantly higher (P < 0.01, P < 0.001, and P < 0.05, respectively) after the HOSO diet than after the EVOO diet. The relationship between the serum cholesterol level (< 6.21 mmol/l or > or = 6.21 mmol/l) and the type of dietary oil on eicosanoids, peroxides and alpha-tocopherol were evaluated by two-way ANOVA. Dietary oil significantly affected (P < 0.05) the PRP-TXB2 level, whereas serum and LDL peroxides were significantly affected (P < 0.001 and P < 0.01, respectively) by the serum cholesterol level. The plasma alpha-tocopherol level was significantly affected by the serum cholesterol level and the type of dietary oil (both P < 0.001). No significant relationships were found between serum cholesterol levels, serum peroxide or LDL peroxide levels, plasma alpha-tocopherol concentrations or alpha-tocopherol intakes with eicosanoid production or the thrombogenic ratio due to dietary changes. However, in spite of their higher alpha-tocopherol levels, hypercholesterolaemic subjects showed increased peroxidation in serum and LDL in comparison with normocholesterolaemic subjects on the HOSO diet in comparison with the EVOO diet. These findings suggest that differences in the type of minor compounds, as well as in the concentration of linoleic acid, in both these monounsaturated oils may play an important role in modulating eicosanoid production and lipoprotein peroxidation when they constitute a large proportion of the diet of post-menopausal women.