Does genotype and equol-production status affect response to isoflavones? Data from a pan-European study on the effects of isoflavones on cardiovascular risk markers in post-menopausal women

The increase in CVD incidence following the menopause is associated with oestrogen loss. Dietary isoflavones are thought to be cardioprotective via their oestrogenic and oestrogen receptor-independent effects, but evidence to support this role is scarce. Individual variation in response to diet may be considerable and can obscure potential beneficial effects in a sample population; in particular, the response to isoflavone treatment may vary according to genotype and equol-production status. The effects of isoflavone supplementation (50hairspmg/d) on a range of established and novel biomarkers of CVD, including markers of lipid and glucose metabolism and inflammatory biomarkers, have been investigated in a placebo-controlled 2x8-week randomised cross-over study in 117 healthy post-menopausal women. Responsiveness to isoflavone supplementation according to (1) single nucleotide polymorphisms in a range of key CVD genes, including oestrogen receptor (ER) alpha and beta and (2) equol-production status has been examined. Isoflavones supplementation was found to have no effect on markers of lipids and glucose metabolism. Isoflavones improve C-reactive protein concentrations but do not affect other plasma inflammatory markers. There are no differences in response to isoflavones according to equol-production status. However, differences in HDL-cholesterol and vascular cell adhesion molecule 1 response to isoflavones v. placebo are evident with specific ER beta genotypes. In conclusion, isoflavones have beneficial effects on C-reactive protein, but not other cardiovascular risk markers. However, specific ER beta gene polymorphic subgroups may benefit from isoflavone supplementation.

UK Food Standards Agency workshop report: the effects of the dietary n-6 : n-3 fatty acid ratio on cardiovascular health

This report summarises a workshop convened by the UK Food Standards Agency (FSA) on 11 September 2006 to review the results of three FSA-funded studies and other recent research on effects of the dietary n-6:n-3 fatty acid ratio on cardiovascular health. The objective of this workshop was to reach a clear conclusion on whether or not it was worth funding any further research in this area. On the basis of this review of the experimental evidence and on theoretical grounds, it was concluded that the n-6:n-3 fatty acid ratio is not a useful concept and that it distracts attention away from increasing absolute intakes of long-chain n-3 fatty acids which have been shown to have beneficial effects on cardiovascular health. Other markers of fatty acid intake, that more closely relate to physiological function, may be more useful.

Effects of chronic and acute fruit and vegetable juice consumption on cardiovascular disease risk factors

Diets low in fruit and vegetables are reportedly responsible for 2.7 million deaths annually from cardiovascular diseases (CVD) and certain cancers. A daily fruit and vegetable intake of five 80 g portions is recommended for chronic disease prevention. However, in the UK, average adult consumption is less than three portions. It is suggested that fruit juice should only count as one portion. However, fruit juices are a beneficial source of phytochemicals. The preliminary results of two randomized, controlled, crossover, dietary intervention studies investigating the effects of chronic and acute consumption of fruit and vegetable puree and juice based drinks (FVPJ) on bioavailability, antioxidant status, vascular reactivity, and risk factors for CVD are reported. In the first study, 39 volunteers consumed 200 ml FVPJ, or fruit-flavoured control, daily for six weeks. In the second study, 24 volunteers consumed 400 mL FVPJ, or sugar-matched control, on the morning of the study day. Blood and urine samples were collected throughout both studies and real-time measurements of vascular tone were performed using laser Doppler imaging with iontophoresis. Overall, the studies showed that the fruit and vegetable puree and juice based drink increased dietary phytochemicals. There was a trend towards increased vasodilation following both acute and chronic fruit juice consumption. Measurements of antioxidant status, oxidative stress and other cardiovascular disease risk factors are currently being determined.

Olive leaf phenolics and cardiovascular risk reduction: Physiological effects and mechanisms of action

Olive oil, an important component of the Mediterranean diet, is rich in polyphenols and is known to possess positive health effects relative to other dietary fats. In addition, the leaves of the olive plant (Olea europaea) contain similar phenolics (oleuropein, luteolin-7-glucoside, apigenin-7-glucoside, verbascoside and hydroxytyrosol) to those of olives and olive oil, although at higher concentrations. For example, the most abundant is the secoiridoid, oleuropein, representing 1–14% of olive leaf weight vs. 0.005–0.12% in olive oil. Although currently considered a waste product of the olive oil industry, recent research has suggested beneficial effects of phenolic-rich olive leaf extracts (OLE) in modifying cardiovascular risk biomarkers such as blood pressure, hyperglycaemia, oxidative stress and inflammation, as well as improving vascular function and lipid profiles. Despite this, data regarding the biological actions of OLE has mostly derived from animal, in vitro and ex vivo studies, with limited evidence deriving from human trials. Although the absorption and metabolism of olive oil phenolics has been investigated, less is known about the bioavailability of phenolics from OLE, limiting the interpretation of existing in vitro and ex vivo data. The current review will begin by describing the phenolic composition of olive leaves in comparison with that of the better studied olive oil. It will then review the effects of OLE on cardiovascular risk factors, covering both animal and human studies and will end by considering potential mechanisms of action

PPARGC1A sequence variation and cardiovascular risk-factor levels: a study of the main genetic effects and gene x environment interactions in children from the European Youth Heart Study.

AIMS/HYPOTHESIS: The PPARGC1A gene coactivates multiple nuclear transcription factors involved in cellular energy metabolism and vascular stasis. In the present study, we genotyped 35 tagging polymorphisms to capture all common PPARGC1A nucleotide sequence variations and tested for association with metabolic and cardiovascular traits in 2,101 Danish and Estonian boys and girls from the European Youth Heart Study, a multicentre school-based cross-sectional cohort study. METHODS: Fasting plasma glucose concentrations, anthropometric variables and blood pressure were measured. Habitual physical activity and aerobic fitness were objectively assessed using uniaxial accelerometry and a maximal aerobic exercise stress test on a bicycle ergometer, respectively. RESULTS: In adjusted models, nominally significant associations were observed for BMI (rs10018239, p = 0.039), waist circumference (rs7656250, p = 0.012; rs8192678 [Gly482Ser], p = 0.015; rs3755863, p = 0.02; rs10018239, beta = -0.01 cm per minor allele copy, p = 0.043), systolic blood pressure (rs2970869, p = 0.018) and fasting glucose concentrations (rs11724368, p = 0.045). Stronger associations were observed for aerobic fitness (rs7656250, p = 0.005; rs13117172, p = 0.008) and fasting glucose concentrations (rs7657071, p = 0.002). None remained significant after correcting for the number of statistical comparisons. We proceeded by testing for gene x physical activity interactions for the polymorphisms that showed nominal evidence of association in the main effect models. None of these tests was statistically significant. CONCLUSIONS/INTERPRETATION: Variants at PPARGC1A may influence several metabolic traits in this European paediatric cohort. However, variation at PPARGC1A is unlikely to have a major impact on cardiovascular or metabolic health in these children.

Crossover study of diets enriched with virgin olive oil, walnuts or almonds. Effects on lipids and other cardiovascular risk markers

Background and aims: Virgin olive oil (VOO) and nuts are basic components of the Mediterranean diet, a heart-healthy dietary pattern. Nuts have well known cholesterol lowering effects, while evidence is unclear for VOO. We designed a study in hypercholesterolemic patients to assess the effects on serum lipids and other intermediate markers of cardiovascular risk of replacing 40% of the fat in the background diet with VOO, walnuts or almonds. Methods and Results: After a 4 week run-in period with a healthy diet, eligible candidates were randomized into three diet sequences in a crossover design, with a common background diet enriched with VOO, walnuts or almonds, lasting 4 weeks each. Outcomes were changes of serum lipids and oxidation and inflammation markers, measured by standard methods. Plasma fatty acids were determined by gas chromatography to assess compliance. In 18 participants completing the study (9 women, mean age 56 y, BMI 25.7 kg/m(2)), LDL-cholesterol was reduced from baseline by 7.3%, 10.8% and 13.4% after the VOO, walnut and almond diets, respectively (P = 0.001, Friedman test). Total cholesterol and LDL/HDL ratios decreased in parallel. LDL-cholesterol decreases were greater than predicted from dietary fatty acid and cholesterol exchanges among diets. No changes of other lipid fractions, oxidation analytes or inflammatory biomarkers were observed. Plasma fatty acid changes after each diet sequence supported good compliance.

Sidestream cigarette smoke effects on cardiovascular responses in conscious rats: involvement of oxidative stress in the fourth cerebral ventricle

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of exercise training on the cardiovascular system: Pharmacological approaches

Physical exercise promotes beneficial health effects by preventing or reducing the deleterious effects of pathological conditions, such as arterial hypertension, coronary artery disease, atherosclerosis, diabetes mellitus, osteoporosis, Parkinson's disease, and Alzheimer disease. Human movement studies are becoming an emerging science in the epidemiological area and public health. A great number of studies have shown that exercise training, in general, reduces sympathetic activity and/or increases parasympathetic tonus either in human or laboratory animals. Alterations in autonomic nervous system have been correlated with reduction in heart rate (resting bradycardia) and blood pressure, either in normotensive or hypertensive subjects. However, the underlying mechanisms by which physical exercise produce bradycardia and reduces blood pressure has not been fully understood. Pharmacological studies have particularly contributed to the comprehension of the role of receptor and transduction signaling pathways on the heart and blood vessels in response to exercise training. This review summarizes and examines the data from studies using animal models and human to determine the effect of exercise training on the cardiovascular system. (c) 2007 Elsevier B.V. All rights reserved.

Effects of the administration of a catalase inhibitor into the fourth cerebral ventricle on cardiovascular responses in spontaneously hypertensive rats exposed to sidestream cigarette smoke

OBJECTIVE: ,,,,,Previous studies have demonstrated a relationship between brain oxidative stress and cardiovascular regulation. We evaluated the effects of central catalase inhibition on cardiovascular responses in spontaneously hypertensive rats exposed to sidestream cigarette smoke. ,,,, ,,,, ,,,,,METHODS: ,,,,,Male Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SH) (16 weeks old) were implanted with a stainless steel guide cannula leading into the fourth cerebral ventricle (4th V). The femoral artery and vein were cannulated for arterial pressure and heart rate measurement and drug infusion, respectively. The rats were exposed to sidestream cigarette smoke for 180 minutes/day, 5 days/week for 3 weeks (CO: 100-300 ppm). The baroreflex was tested using a pressor dose of phenylephrine (8 μg/kg, bolus) and a depressor dose of sodium nitroprusside (50 μg/kg, bolus). Cardiovascular responses were evaluated before and 5, 15, 30 and 60 minutes after injection of a catalase inhibitor (3-amino-1,2,4-triazole, 0.001 g/100 μL) into the 4th V. ,,,, ,,,, ,,,,,RESULTS: ,,,,,Vehicle administration into the 4th V did not affect the cardiovascular response, whereas administration of the central catalase inhibitor increased the basal HR and attenuated the bradycardic peak (p<0.05) to a greater extent in WKY rats exposed to sidestream cigarette smoke than in WKY rats exposed to fresh air. However, in spontaneously hypertensive rats, the effect of the catalase inhibitor treatment was stronger in the fresh air condition (p<0.05). ,,,, ,,,, ,,,,,CONCLUSION: ,,,,,Administration of a catalase inhibitor into the 4th V combined with exposure to sidestream cigarette smoke has a stronger effect in WKY rats than in SH rats.

Effects of remifentanil infusion regimens on cardiovascular function and responses to noxious stimulation in propofol-anesthetized cats

Objective-To evaluate the effects of 2 remifentanil infusion regimens on cardiovascular function and responses to nociceptive stimulation in propofol-anesthetized cats.Animals-8 adult cats.Procedures-On 2 occasions, cats received acepromazine followed by propofol (6 mg/kg then 0.3 mg/kg/min, IV) and a constant rate infusion (CRI) of remifentanil (0.2 or 0.3 mu g/kg/min,IV) for 90 minutes and underwent mechanical ventilation (phase I). After recording physiologic variables, an electrical stimulus (50 V; 50 Hz; 10 milliseconds) was applied to a forelimb to assess motor responses to nociceptive stimulation. After an interval (>= 10 days), the same cats were anesthetized via administration of acepromazine and a similar infusion regimen of propofol; the remifentanil infusion rate adjustments that were required to inhibit cardiovascular responses to ovariohysterectomy were recorded (phase II).Results-In phase I, heart rate and arterial pressure did not differ between remifentanil-treated groups. From 30 to 90 minutes, cats receiving 0.3 mu g of remifentanil/kg/min had no response to noxious stimulation. Purposeful movement was detected more frequently in cats receiving 0.2 mu g of remifentanil/kg/min. In phase II, the highest dosage (mean +/- SEM) of remifentanil that prevented cardiovascular responses was 0.23 +/- 0.01 mu g/kg/min. For all experiments, mean time from infusion cessation until standing ranged from 115 to 140 minutes.Conclusions and Clinical Relevance-Although the lower infusion rate of remifentanil allowed ovariohysterectomy to be performed, a CRI of 0.3 mu g/kg/min was necessary to prevent motor response to electrical stimulation in propofol-anesthetized cats. Recovery from anesthesia was prolonged with this technique.

Effects of acepromazine on the cardiovascular actions of dopamine in anesthetized dogs

To evaluate the effects of acepromazine maleate on the cardiovascular changes induced by dopamine in isoflurane-anesthetized dogs.Prospective, randomized cross-over experimental design.Six healthy adult spayed female dogs weighing 16.4 +/- 3.5 kg (mean +/- SD).Each dog received two treatments, at least 1 week apart. Acepromazine (0.03 mg kg(-1), IV) was administered 15 minutes before anesthesia was induced with propofol (7 mg kg(-1), IV) and maintained with isoflurane (1.8% end-tidal). Acepromazine was not administered in the control treatment. Baseline cardiopulmonary parameters were measured 90 minutes after induction. Thereafter, dopamine was administered intravenously at 5, 10, and 15 mu g kg(-1) minute(-1), with each infusion rate lasting 30 minutes. Cardiopulmonary data were obtained at the end of each infusion rate.Dopamine induced dose-related increases in cardiac index (CI), stroke index, arterial blood pressure, mean pulmonary arterial pressure, oxygen delivery index (DO2I) and oxygen consumption index. In the control treatment, systemic vascular resistance index (SVRI) decreased during administration of 5 and 10 mu g kg(-1) minute(-1) of dopamine and returned to baseline with the highest dose (15 mu g kg (-1) minute(-1)). After acepromazine treatment, SVRI decreased from baseline during dopamine administration, regardless of the infusion rate, and this resulted in a smaller increase in blood pressure at 15 mu g kg (-1) minute(-1). During dopamine infusion hemoglobin concentrations were lower following acepromazine and this contributed to significantly lower arterial O-2 content.Acepromazine prevented the return in SVRI to baseline and reduced the magnitude of the increase in arterial pressure induced by higher doses of dopamine. However, reduced SRVI associated with lower doses of dopamine and the ability of dopamine to increase CI and DO2I were not modified by acepromazine premedication.Previous acepromazine administration reduces the efficacy of dopamine as a vasopressor agent in isoflurane anesthetized dogs. Other beneficial effects of dopamine such as increased CO are not modified by acepromazine.

Effects of Jugular Vein Occlusion on Cardiovascular Parameters in Horses During Exercise on a Treadmill

The purpose of the present investigation was to examine the effects of unilateral and bilateral jugular vein occlusion by temporary surgical ligature on the heart rate and arterial and venous blood pressure in sedentary horses during progressive treadmill exercise. Six horses performed three exercise tests (ET). ET1, considered the control, was performed in horses without jugular occlusions. ET2 and ET3 were performed with unilateral and bilateral occlusion by temporary surgical ligature of the jugular veins, respectively. Heart rate, arterial pressure, and pressure of the occluded jugular vein were evaluated. Clinically, the horses presented apathy, head edema, congested mucous membranes, increased capillary refill time, and dysphagia. These signs were observed with the unilateral jugular vein occlusion and became more evident with the bilateral occlusion. Comparing ETs, no differences were observed in heart rate. However, jugular occlusions promoted a decrease in the mean arterial pressure and a severe increase in jugular pressure. Head edema caused by the jugular vein occlusion in the horses could interfere with the autonomic cardiovascular regulation of arterial blood pressure during exercise, likely leading to an impairment of tissue perfusion. Jugular occlusion, even unilateral, also causes severe head venous congestion, leading to venous hypertension that was aggravated by exercise, which could risk development of cerebral edema and neurological damage. The present results obtained from sedentary horses are preliminary data that lead us to suggest that sport horses presenting jugular occlusive thrombophlebitis, even unilateral, may be prevented from performing athletic activities. © 2013 Elsevier Inc. All rights reserved.

Immediate and long-term effects of psychological stress during adolescence in cardiovascular function: comparison of homotypic vs heterotypic stress regimens

Adolescence has been proposed as an ontogenic period of vulnerability to stress. Nevertheless, the impact of stressful events during adolescence in cardiovascular activity is poorly understood. Therefore, the purpose of this study was to investigate the immediate and long-lasting effects of exposure to stressful events during adolescence in cardiovascular function of rats. To this end, we compared the impact of 10-days exposure to two chronic stress protocols: the repeated restraint stress (RRS, homotypic) and chronic variable stress (CVS, heterotypic). Independent groups of animals were tested 24 h (immediate) or three weeks (long-lasting) following completion of stress period. Exposure to CVS, but not RRS, during adolescence increased basal HR values without affecting arterial pressure, which was followed by augmented power of oscillatory component at low frequency (sympathetic-related) of the pulse interval (PI). RRS enhanced variance of the PI with an increase in the power of both low and high (parasympathetic-related) frequency components. RRS also increased the baroreflex gain. Neither RRS nor CVS affected systolic arterial pressure variability. The RRS-evoked changes in PI variability were long-lasting and persisted into adulthood while all alterations evoked by the CVS were reversed in adulthood. These findings indicate a stress type-specific influence in immediate and long-term effects of stress during adolescence in cardiovascular function. While immediate changes in cardiovascular function were mainly observed following CVS, long-lasting autonomic consequences in adulthood were observed only in animals exposed to RRS during adolescence.

Effects of nitric oxide synthesis inhibitor or fluoxetine treatment on depression-like state and cardiovascular changes induced by chronic variable stress in rats

Comorbidity between mood disorders and cardiovascular disease has been described extensively. However, available antidepressants can have cardiovascular side effects. Treatment with selective inhibitors of neuronal nitric oxide synthase (nNOS) induces antidepressant effects, but whether the antidepressant-like effects of these drugs are followed by cardiovascular changes has not been previously investigated. Here, we tested in male rats exposed to chronic variable stress (CVS) the hypothesis that nNOS blockers are advantageous compared with conventional antidepressants in terms of cardiovascular side effects. We compared the effects of chronic treatment with the preferential nNOS inhibitor 7-nitroindazole (7-NI) with those evoked by the conventional antidepressant fluoxetine on alterations that are considered as markers of depression (immobility in the forced swimming test, FST, decreased body weight gain and increased plasma corticosterone concentration) and cardiovascular changes caused by CVS. Rats were exposed to a 14-day CVS protocol, while being concurrently treated daily with either 7-NI (30 mg/kg) or fluoxetine (10 mg/kg). Fluoxetine and 7-NI prevented the increase in immobility in the FST induced by CVS and reduced plasma corticosterone concentration in stressed rats. Both these treatments also prevented the CVS-evoked reduction of the depressor response to vasodilator agents and baroreflex changes. Fluoxetine and 7-NI-induced cardiovascular changes independent of stress exposure, including cardiac autonomic imbalance, increased intrinsic heart rate and vascular sympathetic modulation, a reduction of the pressor response to vasoconstrictor agents, and impairment of baroreflex activity. Altogether, these findings provide evidence that fluoxetine and 7-NI have similar effects on the depression-like state induced by CVS and on cardiovascular function.