Baroreflex sensitivity and central hemodynamics after omega-3 polyunsaturated fatty acids supplementation in an animal model of menopause.

OBJECTIVE: Baroreflex sensitivity (BRS) and central arterial function are significantly worsened after menopausal transition. This study tested the hypothesis that administration of n-3 polyunsaturated fatty acids (n-3 PUFA) might contribute to prevent these adverse changes in the vascular function of ovariectomized rats, an animal model of experimental menopause. METHODS: We randomized 30 female Wistar rats, 2months old, into 3 groups: control (CTRL), sham surgery, normal diet; ovariectomized with normal diet (OVX) and ovariectomized with n-3 PUFA supplementation by daily gavage (0.8g/kg/d) (OVX+O3). Two months after surgery, BRS was calculated as the bradycardic response to phenylephrine-induced blood pressure increase, while large artery function was estimated by the graphical analysis of the aortic pressure wave (diastolic to systolic pressure-time integral ratio, DTI/STI). RESULTS: Ovariectomy caused a significant decrease in BRS (CTRL: 6.23±0.68ms/mmHg; OVX: 2.85±0.75; p<0.001). n-3 PUFA supplementation prevented part of the decline of BRS caused by surgical menopause (OVX+O3: 4.75±0.53; p<0.01 vs OVX). In animals treated with n-3 PUFA, the central arterial pressure profile did not show the changes in DTI/STI ratio seen in OVX (OVX: 3.31±1.72; OVX+O3: 3.83±1.52; p<0.01). CONCLUSIONS: In an experimental model of menopause, treatment with n-3 PUFA normalized central hemodynamics and prevented the decrease in BRS, associated with the reduction of compliance of the arterial wall. These findings suggest a therapeutic benefit of n-3 PUFA supplementation in the prevention of postmenopausal vascular disease.

Hypovitaminosis D and organ damage in patients with arterial hypertension: a multicenter double blind randomised controlled trial of cholecalciferol supplementation (HYPODD) : study design, clinical procedures and treatment protocol.

INTRODUCTION: At this time, good quality randomized clinical trials assessing the effects of vitamin D supplementation on cardiometabolic outcomes are lacking in the international literature. AIM: To fill this gap, the Working Group on Vitamin D and Cardiorenal Disorders established jointly by the Italian Society of Hypertension (SIIA) and the Forum in Bone and Mineral Research conceived the HYPODD study (HYPOvitaminosis D and organ Damage). METHODS: HYPODD is a no-profit multicenter 12-month parallel-group double-blind placebo controlled randomized trial aiming to assess the effects of cholecalciferol supplementation on blood pressure control, antihypertensive drugs consumption and progression of target organ damage in patients with essential hypertension and 25-hydroxyvitamin D serum level lower than 20 ng/ml (vitamin D deficiency). HYPODD is coordinated by the European Society Excellence Center of Hypertension of Federico II University, Naples, and involves 12 academic institutions in Italy (Ancona, Milan, Padua, Perugia, Rome, Siena, Trieste, Turin, Udine, Varese, and Verona). RESULTS AND CONCLUSION: The HYPODD study has been registered at the Agenzia Italiana del Farmaco-Osservatorio sulla Sperimentazione Clinica del Farmaco (AIFA-OsSC) and EUDRACT sites (n° 2012-003514-14) and has been approved by the Ethical Committees of all the Centers involved in the study. The patients' recruitment is currently underway.

Supplementation of omega-3 polyunsaturated fatty acids prevents increase in arterial stiffness after experimental menopause.

BACKGROUND: Menopause is associated with increased arterial stiffness, an independent marker of cardiovascular risk. Omega-3 polyunsaturated fatty acids (N3-PUFAs) are thought to have multiple cardiovascular benefits, including prevention of arterial stiffness. We investigated whether treatment with N3-PUFA prevents increase in arterial stiffness in ovariectomized rats, an animal model of experimental menopause. METHODS: A total of 43 Wistar rats, 2 months old, were divided into 3 groups, control, sham surgery, normal diet (CTRL, n = 15); ovariectomy, normal diet (OVX, n = 14); and ovariectomy with N3-PUFA supplementation (0.8 g/kg/d in daily gavages administration; OVX + O3, n = 14). Two months after surgery, carotid-femoral pulse wave velocity (PWV) and arterial blood pressure (BP) were measured by carotid and femoral cannulation. Aortic morphometric measurements were performed after dissection. RESULTS: Ovariectomy caused a significant increase in BP (P < .05), PWV (P < .0001), and elastic modulus (P = .001) compared to CTRL. After ovariectomy, N3-PUFA supplementation completely prevented increase in arterial stiffness (P < .0001 vs OVX) and BP (P < .05 vs OVX) and resulted in a significant increase in body weight and aortic thickness. CONCLUSIONS: In an experimental model of menopause, N3-PUFA supplementation prevents arterial stiffening and other vascular changes induced by ovariectomy. These results represent a therapeutic benefit of N3-PUFAs in prevention of postmenopausal cardiovascular disease.

Treatment with n-3 polyunsaturated fatty acids reverses endothelial dysfunction and oxidative stress in experimental menopause.

Menopause is associated with endothelial dysfunction and oxidative stress. In this condition, reduced n-3 polyunsaturated fatty acids (n-3 PUFAs) contribute to cardiovascular disease. We investigated whether treatment with n-3 PUFA reverses endothelial dysfunction and oxidative stress in experimental menopause. Thirty female rats underwent either sham-surgery or bilateral ovariectomy or bilateral ovariectomy+oral n-3 PUFA (0.8 g kg(-1) day(-1) for 2 months). Ovariectomy caused endothelial dysfunction to acetylcholine, which was reversed by superoxide scavenger Tiron. Erythrocyte membrane lipid composition was characterized by reduced n-3 PUFA total content and omega-3 index, and by concomitant increase in n-6:n-3 PUFA ratio. Ovariectomy-related oxidative stress, demonstrated by both enhanced superoxide production and 3-nitrotyrosine expression in aorta, was associated with increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit NOX-4 protein expression. Endothelial nitric oxide synthase (eNOS) functional inhibition by l-NG-nitroarginine methyl ester, protein expression and activity did not change. In ovariectomized rats, treatment with n-3 PUFA increased n-3 PUFA total content and omega-3 index and decreased n-6:n-3 PUFA ratio in erythrocyte membrane, reversed vascular oxidative stress, endothelial dysfunction, aortic 3-nitrotyrosine and markedly lowered NOX-4 protein expression; eNOS protein expression also increased, paralleled by reversal of inhibitory binding to Caveolin-1, while ex-vivo functional inhibition and NOS synthesis were unchanged. These findings demonstrate in vivo a therapeutic benefit of n-3 PUFA on menopause-associated endothelial dysfunction by reversal of alterations in membrane lipid composition induced by ovariectomy and by reduction of vascular oxidative stress. In this setting they also identify NOX-4 as a potential target to reduce oxidative stress-mediated vascular complications.

[Effects of ramipril and simvastatin on the oxidative stress of diabetic rats]. / Efeito do ramipril e da sinvastatina sobre o estresse oxidativo de ratos diabéticos.

OBJECTIVE: To evaluate if ramipril, with or without simultaneous use of simvastatin, would be capable of reducing oxidative stress of streptozotocin (STZ) induced diabetic rats. METHODS: The drugs were given to the diabetic rats for 2 weeks; oxidative stress was measured by dosage of total plasma antioxidant capacity (TRAP) and malondialdehyde (MDA). RESULTS: Ramipril, used alone, was capable of significantly increasing the antioxidative defenses of the diabetic rat; simvastatin, given alone or combined with ramipril in separate administrations, did not produce any significant effect on the oxidative stress; concomitant administration of ramipril and simvastatin significantly reduced the antioxidative plasmatic defenses of rats with chemically induced diabetes mellitus CONCLUSIONS: Our data corroborate the positive effect of ramipril upon plasma antioxidative defenses but did not confirm a possible beneficial effect of simvastatin in the model. More research is needed to clarify the paradoxal TRAP reduction verified with simultaneous administration of the drugs.

Efeito do ramipril e da sinvastatina sobre o estresse oxidativo de ratos diabéticos / Effects of ramipril and simvastatin on the oxidative stress of diabetic rats

OBJETIVO: Avaliar se o ramipril, isoladamente ou em combinação com a sinvastatina, seria capaz de reduzir o estresse oxidativo de ratos diabéticos pela estreptozotocina (STZ). MÉTODOS: As drogas foram administradas a ratos diabéticos por duas semanas; o estresse oxidativo foi medido por dosagem de capacidade antioxidante total plasmática (TRAP) e malonaldeído (MDA). RESULTADOS: O ramipril usado isoladamente foi capaz de aumentar significativamente as defesas antioxidantes do rato diabético; a sinvastatina isoladamente ou combinada ao ramipril em tomadas separadas não produziu efeito significativo sobre o estresse oxidativo; a administração simultânea de ramipril e sinvastatina reduziu as defesas antioxidantes plasmáticas de ratos com diabetes melito químico. CONCLUSÕES: Os dados do presente estudo corroboram o efeito positivo do ramipril sobre a defesa antioxidante do plasma, mas não confirmam um possível efeito benéfico da sinvastatina no modelo. Pesquisas adicionais são necessárias para clarificar a paradoxal redução da TRAP verificada pela administração simultânea das drogas.

OBJECTIVE: To evaluate if ramipril, with or without simultaneous use of simvastatin, would be capable of reducing oxidative stress of streptozotocin (STZ) induced diabetic rats. METHODS: The drugs were given to the diabetic rats for 2 weeks; oxidative stress was measured by dosage of total plasma antioxidant capacity (TRAP) and malondialdehyde (MDA). RESULTS: Ramipril, used alone, was capable of significantly increasing the antioxidative defenses of the diabetic rat; simvastatin, given alone or combined with ramipril in separate administrations, did not produce any significant effect on the oxidative stress; concomitant administration of ramipril and simvastatin significantly reduced the antioxidative plasmatic defenses of rats with chemically induced diabetes mellitus CONCLUSIONS: Our data corroborate the positive effect of ramipril upon plasma antioxidative defenses but did not confirm a possible beneficial effect of simvastatin in the model. More research is needed to clarify the paradoxal TRAP reduction verified with simultaneous administration of the drugs.

Association between soy and green tea (Camellia sinensis) diminishes hypercholesterolemia and increases total plasma antioxidant potential in dyslipidemic subjects.

OBJECTIVE: To evaluate the hypolipemic and antioxidant effects of soy and green tea alone and/or in association in dyslipidemic subjects. METHODS: One hundred dyslipidemic individuals were allocated into four groups. The soy group ingested 50 g of soy (kinako) daily, and the green tea group ingested 3 g of green tea in 500 mL of water per day. A third group ingested 50 g of soy and 3 g of green tea daily, and the control group had a hypocholesterolemic diet. Evaluations were performed at baseline and after 45 and 90 d. Plasma levels of total cholesterol, high-density lipoprotein, and triacylglycerols were evaluated by automated methods. Low-density lipoprotein (LDL) cholesterol was calculated using the Friedewald equation. LDL was isolated by ultracentrifugation. Total plasma antioxidant capacity and plasma levels of total lipid hydroperoxides and those linked to LDL were evaluated by chemiluminescence. The results were expressed as median values and their 25th to 75th percentiles, with a 5% level of significance. RESULTS: No significant difference occurred in LDL, high-density lipoprotein cholesterol, and triacylglycerol levels across groups. However, a statistically significant difference in total cholesterol occurred within the soy/green tea group 45 and 90 d after intervention. No statistically significant difference occurred in plasma levels of lipid hydroperoxides or those linked to LDL in any of the groups studied. All the groups that used soy and/or green tea presented increased total plasma antioxidant potential. CONCLUSION: Soy and green tea, alone or in combination, increased the total antioxidant potential of hypercholesterolemic patients, whereas only the combination decreased total cholesterol levels.