Biomedical subjects

Maria Alvarez de Sotomayor

Publications and source records attributed to Maria Alvarez de Sotomayor.

6 recordsLinked to original sources

PubMed2006

Fenofibrate improves age-related endothelial dysfunction in rat resistance arteries.

This study was designed to test the hypothesis that fenofibrate, the peroxisome proliferator-activated receptor alpha (PPARalpha) activator, improves age-related endothelial dysfunction in small mesenteric arteries (SMA). Adult and aged rats were treated with fenofibrate and then endothelium-dependent relaxations of SMA; expressions of endothelial NO synthase (eNOS), cyclo-oxygenase (COX-1 and COX-2) and superoxide dismutases (SOD) (Cu/Zn SOD, Mn SOD and EC SOD) proteins and release of TXB(2) and 6-keto-PGF(1alpha) were assessed. Fenofibrate improved endothelium-dependent vasodilatation of arteries from old rats and decreased participation of endothelial vasoconstrictor products, sensitive to COX-1 and COX-2 inhibitors and acting on Tp receptor. Fenofibrate decreased expressions of COX-1 and COX-2, and generation of TXA(2). Release of vasodilator PGI(2) and U46619-induced contraction remained unaltered. Neither NO-mediated vasodilatation nor eNOS expression was affected. The addition of the scavengers, SOD and catalase increased relaxation only in SMA from control rats. Finally, fenofibrate did not change expressions of Cu/Zn SOD and Mn SOD but it increased EC SOD towards that observed in arteries from adult rats. Fenofibrate improves endothelial function in resistance arteries from aged rats by decreasing expression of COX-1 and COX-2 together with enhancing anti-oxidant capacity of the vessel wall probably through the increased expression of EC SOD. This study provides evidence that PPARalpha may have clinical applications toward maintaining endothelial function during ageing.

Aging↗

PubMed2005

L-carnitine and propionyl-L-carnitine improve endothelial dysfunction in spontaneously hypertensive rats: different participation of NO and COX-products.

L-carnitine and propionyl-L-carnitine are supplements to therapy in cardiovascular pathologies. Their effect on endothelial dysfunction in hypertension was studied after treatment with either 200 mg/kg of L-carnitine or propionyl-L-carnitine during 8 weeks of spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). Endothelial function was assessed in aortic rings by carbachol-induced relaxation (CCh 10(-8) to 10(-4) M) and factors involved were characterized in the presence of the inhibitors: L-NAME, indomethacin, the TXA2/PGH2 Tp receptor antagonist ICI-192,605 and the thromboxane synthetase inhibitor-Tp receptor antagonist, Ro-68,070. The effect on phenylephrine-induced contractions was also observed. To identify the nature of vasoactive COX-derived products, enzyme-immunoassay of incubation media was assessed. Involvement of reactive oxygen species was evaluated by incubating with superoxide dismutase and catalase. Nitric oxide production was evaluated by serum concentration of NO2+NO3.Treatment with both compounds improved endothelial function of rings from SHR without blood pressure change. Propionyl-L-carnitine increased NO participation in WKY and SHR. L-carnitine reduced endothelium-dependent responses to CCh in WKY due to an increase of TXA2 production. In both SHR and WKY, L-carnitine enhanced concentration of PGI2 and increased participation of NO. Results in the presence of SOD plus catalase show that it might be related to antioxidant properties of L-carnitine and propionyl-L-carnitine. Comparison between the effect of both compounds shows that both may reduce reactive oxygen species and increase NO participation in endothelium-dependent relaxations in SHR. However, only L-carnitine was able to increase the release of the vasodilator PGI2 and even enhanced TXA2 production in normotensive rats.

Administration, Oral↗

PubMed2005

Improvement of age-related endothelial dysfunction by simvastatin: effect on NO and COX pathways.

The effects of oral administration of the HMG-CoA reductase inhibitor, simvastatin (SV), on age-related endothelial dysfunction were investigated in the aorta of male Wistar rats. Adult (12-14 weeks) and old (60-80 weeks) rats were treated daily for 12 weeks with either vehicle or SV (1 mg kg(-1)). In old rats, SV treatment did not significantly affect systolic blood pressure and LDL-cholesterol, but it reduced plasma cholesterol, triglycerides and oxidised LDL though it did not affect total antioxidant status. SV improved endothelium-dependent relaxation to acetylcholine and A-23187 in vessels from aged, but not adult, rats. This effect was linked to a greater NO vasodilatation via an increased expression of endothelial NO-synthase. A mechanism sensitive to superoxide dismutase and catalase also accounts for enhanced endothelial vasodilatation. Finally, SV did not affect the release of prostacyclin, but it inhibited the generation of thromboxane (TX) A2 from COX-2 isoform. The effect of the latter was sensitive to the Tp receptor antagonist, ICI-192,605. The present study provides evidence that oral administration of SV improves endothelial dysfunction in the aorta from aged rats by mechanisms associated with enhanced NO vasodilatation, reduced release of TXA2 from cyclo-oxygenase, and increased antioxidant properties of the vessel wall. These data underscore a new therapeutic perspective for SV in age-related endothelial dysfunction.

Acetylcholine↗

PubMed2004

Argan (Argania spinosa) oil lowers blood pressure and improves endothelial dysfunction in spontaneously hypertensive rats.

Traditionally hand-pressed argan oil, obtained from Argania spinosa seeds, is eaten raw in south-west Morocco; its rich composition of tocopherols, MUFA and PUFA make a study of its actions on risk factors for CVD, such as hypertension, interesting. The effects of 7 weeks of treatment with argan oil (10 ml/kg) on the blood pressure and endothelial function of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats were investigated. Systolic blood pressure and heart rate were measured every week by the tail-cuff method and endothelial function was assessed by carbachol (10(-8) to 10(-4) M)-induced relaxations of aortic rings and small mesenteric arteries pre-contracted with phenylephrine. Argan-oil administration reduced the mean blood pressure of SHR after the fifth week of treatment (P<0.05) and increased (P<0.01) the endothelial responses of arteries from SHR. The NO synthase inhibitor, L-N-omega-nitroarginine (3 x 10(-5) M) revealed a greater participation of NO in the relaxant effect after the treatment. When cyclooxygenase (COX) was blocked with indomethacin (10(-5) M), an involvement of COX products in the endothelium-dependent response was characterized. Enzyme immunoassay of thromboxane B2 showed a significant decrease (P<0.05) in the release of thromboxane A2 in both aorta and small mesenteric artery after argan-oil treatment of SHR. Experiments in the presence of the thromboxane A2-prostaglandin H2 receptor antagonist ICI 192,605 (10(-5) M) confirmed this result. Results after incubation with the antioxidants superoxide dismutase and catalase suggested that a decreased oxidative stress might contribute to explain the beneficial effects of argan-oil treatment.

Animals↗

PubMed2003

Preservation of vascular contraction during ageing: dual effect on calcium handling and sensitization.

(1) The present study was aimed to characterize the effects of ageing on vascular contraction by noradrenaline in rat isolated arteries. The existence of vascular bed heterogeneity was investigated in endothelium-denuded conductance (aorta) and resistance (small mesenteric artery, SMA) arteries, with respect to Ca(2+) handling, Ca(2+) sensitization or Ca(2+)-independent mechanisms. (2) In both arteries, contractions to noradrenaline were not different between adult and aged rats. (3) In Ca(2+)- free medium, noradrenaline elicited a transient increase in tension that was reduced by the Ca(2+) mobilizing agents, ryanodine and thapsigargin, in arteries from adult rats. A loss of the thapsigargin- but not the ryanodine-sensitive component of noradrenaline-induced contraction was observed in the two arteries from aged rats. (4) After depletion of Ca(2+) stores with noradrenaline, addition of exogenous CaCl(2) produced a sustained contraction that was decreased to the same extent by the protein kinase C inhibitor, GF 109203X and the tyrosine kinase inhibitor, tyrphostin A-23, in arteries from adult and aged rats. The Rho-associated protein kinase inhibitor, Y-27632, caused identical relaxation of noradrenaline pre-contracted arteries from both age groups. (5) Basal intracellular calcium ([Ca(2+)](i)) was higher in SMA from aged than from adult rats. In addition, the noradrenaline [Ca(2+)](i)-force relationship was significantly shifted to the right in the SMA from aged rats. (6) Altogether, these data indicate that responsiveness to noradrenaline is preserved both in conductance and resistance arteries with ageing. The latter results from the association of increased basal [Ca(2+)](i), changes in Ca(2+) handling at the level of thapsigargin-sensitive sarcoplasmic reticulum Ca(2+)-ATPases and decreased myofilament sensitivity to Ca(2+).

Aging↗

PubMed2002

Simvastatin improves endothelial function in spontaneously hypertensive rats through a superoxide dismutase mediated antioxidant effect.

BACKGROUND: Hydroxymethylglutaryl coenzyme A (HMGCoA) reductase inhibitors have beneficial effects beyond their cholesterol-lowering properties. The antioxidant mechanism of HMGCoA reductase inhibitors is not completely understood. OBJECTIVES: To elucidate the antioxidant effect of simvastatin. METHODS: We studied the influence of simvastatin treatment on the development of hypertension, modification of antioxidant systems, and reactivity of aortic rings in Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. RESULTS: Simvastatin had no effect on blood pressure (BP). Simvastatin treatment (either 1 or 2 mg/kg body weight for 12 or 20 weeks) increased superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in SHR rats compared with untreated control SHR rats. Carbachol-induced relaxation of aortic rings was impaired in control SHR rats and was restored by simvastatin treatment. Addition of SOD improved the response in control SHR rats and did not have any effect in treated SHR rats. Addition of diethyldithiocarbamic acid, a selective inhibitor of SOD, produced a mild non-significant impairment in carbachol-induced relaxation in control SHR rats, suggesting a deficient antioxidant system in these animals. However, in treated SHR and in WKY rats, impairment of the relaxation was marked, implying that SOD activity in these animals was important to maintain endothelial function. In aortic rings without endothelium from SHR rats, contraction induced by free radicals was substantially higher than in WKY rats. This effect was attenuated in 1-mg-treated rats and abolished in 2-mg-treated rats. CONCLUSIONS: Simvastatin promotes intracellular antioxidant systems, fundamentally SOD, restoring endothelial function but not having any effect on blood pressure.

Animals↗