Biomedical subjects

Alexandra Oudot

Publications and source records attributed to Alexandra Oudot.

7 recordsLinked to original sources

PubMed2006

NADPH oxidases are in part responsible for increased cardiovascular superoxide production during aging.

The aim of our study was to examine in rats, age-related differences in myocardial ischemic recovery and to determine the possible relationship with modification of cardiac and vascular oxidative stress. Isolated perfused hearts from young (2 months), adult (6 months), and old (21 months) Wistar rats were subjected to a ischemia-reperfusion sequence. Vascular histomorphological analyses were performed and NADPH oxidase was studied. The expression of angiotensin AT(1) receptors was evaluated using immunostaining. During the preischemic period, but also after ischemia, an aged-related decrease in myocardial functional parameters was observed, and was associated with an increased release of reactive oxygen species. In aortas, the activity and expression of NADPH oxidase increased with age according to the ESR, fluorescence microscopy, and immunohistochemistry; the NADPH oxidase involved was localized in endothelial cells. We found an age-related increase in the expression of endothelial angiotensin AT(1). Our study suggests that myocardial function and adaptation to ischemia-reperfusion declined during aging and are related to a higher level of oxidative stress. Endothelial NADPH oxidase is a major contributor to age-related cardiovascular deterioration. One of the regulators of vascular NADPH oxidase activity, the renin-angiotensin system, may be involved in the modulation of vascular superoxide production during the aging process.

Adaptation, Physiological↗

PubMed2006

Dissociation between vascular oxidative stress and cardiovascular function in Wistar Kyoto and spontaneously hypertensive rats.

It has not been completely demonstrated if hypertension may, in part, develop as a result of increased oxidative stress (OS), inflammation and little is known about the short-term effects of antioxidant therapy. This study was designed to appreciate the effect of 7 days vitamin C-enriched diet (5 g/kg/day) on hemodynamic function and vascular OS in normotensive Wistar Kyoto rats and hypertensive rats (SHR). Aorta NAD(P)H oxidase activity was determinate and free radicals evaluated by electron spin resonance with a spin probe CP-H. Matrix metalloproteinase-1 (MMP-1) and monocyte chemoattractant protein-1 (MCP-1) expression were measured. The treatment with vitamin C did not change arterial pressure in SHR but prevented the increase in OS levels in SHR aortas. MMP-1 and MCP-1 expressions were more intense in the media of SHR aortas than in those of WKY rats but these expressions were not modified by vitamin C-pretreatment. Vitamin C-pretreatment was not able to protect heart against in vitro ischemia-reperfusion dysfunctions. These data may suggest that treatment with high doses of vitamin C in SHR can limit over-production of reactive oxygen species; however this effect was not accompanied with changes in arterial pressure and protection against I-R dysfunctions. Dissociation between vascular oxidative stress and cardiovascular function may be evoked.

Animals↗

PubMed2006

Erectile dysfunction in hypercholesterolemic atherosclerotic apolipoprotein E knockout mice.

INTRODUCTION: Erectile dysfunction (ED) and cardiovascular diseases share the same risk factors. Although the use of hypercholesterolemic rabbit models has proven to be useful to illustrate the link between ED and hypercholesterolemia, the cost of daily maintenance of the animals and necessity for important amounts of drug have limited their use. AIM: We aimed to develop a new model of atherosclerosis-associated ED in a well-known experimental model of atherosclerosis, the apolipoprotein E knockout (ApoE KO) mouse. METHODS: Erectile function was evaluated by recording frequency-dependent increases in intracavernous pressure following electrical stimulation of the cavernous nerve in 26-, 32-, and 38-week-old ApoE KO mice fed a Western-type diet and age-matched C57BL6/J anesthetized mice. Atherosclerotic lesions were evaluated by planimetry in oil red O-stained aortas. RESULTS: We found that in contrast to C57BL6/J mice, ApoE mice displayed atherosclerotic lesions covering 22% of the aortic luminal surface at 26 weeks of age and increasing to 27% and 35% at 32 weeks and 38 weeks of age, respectively. The amplitude of erectile responses to electrical stimulation of the cavernous nerve was markedly impaired in 26-week-old ApoE KO mice as compared with age-matched C57BL6/J mice. Impairment in erectile function persisted in ApoE KO mice 32 and 38 weeks of age. CONCLUSIONS: The ApoE KO mouse, a well-characterized model to study disorders associated with hypercholesterolemia and atherosclerosis in cardiovascular research, could therefore be suitable for investigation of disease-modifying effects of new therapeutic strategies aiming to target both atherosclerosis and ED.

Animals↗

PubMed2005

Prevalence and impact of metabolic syndrome on hospital outcomes in acute myocardial infarction.

BACKGROUND: The impact of metabolic syndrome after acute myocardial infarction (AMI) has not yet been studied. In a population-based sample of patients with AMI, we sought to determine the prevalence of metabolic syndrome in patients with AMI, its impact on hospital outcomes, and to assess the relative influence of each of the components of the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III definition of metabolic syndrome on the risk of death and heart failure. METHODS: A total of 633 unselected, consecutive patients hospitalized with AMI were categorized according to the NCEP ATP III metabolic syndrome criteria (presence of >/=3 of the following: hyperglycemia; triglyceride level >/=150 mg/dL [>/=1.7 mmol/L]; high-density lipoprotein cholesterol level <40 mg/dL [<1.04 mmol/L] in men and <50 mg/dL [<1.30 mmol/L] in women; blood pressure >/=130/85 mm Hg; and waist circumference >102 cm in men or 88 cm in women). RESULTS: Among the 633 patients, 290 (46%) fulfilled the criteria for metabolic syndrome. Patients with metabolic syndrome were older and more likely to be women. Acute myocardial infarction characteristics and left ventricular ejection fraction rates were similar for both groups. In-hospital case fatality was higher in patients with metabolic syndrome compared with those without, as was the incidence of severe heart failure (Killip class >II). In multivariate analysis, metabolic syndrome was a strong and independent predictor of severe heart failure, but not in-hospital death. Analysis of the predictive value of each of the 5 metabolic syndrome components for severe heart failure showed that hyperglycemia was the major determinant (odds ratio, 3.31; 95% confidence interval, 1.86-5.87). CONCLUSIONS: In an unselected population of patients with AMI, the prevalence of metabolic syndrome was high. Metabolic syndrome appeared associated with worse in-hospital outcome, with a higher risk of development of severe heart failure. Among metabolic syndrome components, hyperglycemia was the main correlate of the risk of development of severe heart failure during AMI.

Aged↗

PubMed2005

Transient reduction in myocardial free oxygen radical levels is involved in the improved cardiac function and structure after long-term allopurinol treatment initiated in established chronic heart failure.

AIMS: Oxidative stress, i.e. imbalance between reactive oxygen species (ROS) and antioxidant defences, contributes to the progression of chronic heart failure (CHF). Acute inhibition of xanthine oxidase (XO), which produces ROS, improves mechanical efficiency of the failing heart, but whether long-term XO inhibition exerts beneficial effects in CHF is unknown. METHODS AND RESULTS: In rats with established CHF induced by left coronary ligation, we assessed the effects of a 5-day and a 10-week treatment with the XO inhibitor allopurinol (50 mg kg(-1) day(-1)) on haemodynamics and left ventricular (LV) function and structure. Both acute and chronic allopurinol treatment increase cardiac output without modification of arterial pressure, but only chronic allopurinol treatment reduces LV end-diastolic pressure and LV relaxation constant. Chronic allopurinol treatment decreases both LV systolic and diastolic diameters, but acute allopurinol treatment only decreases LV systolic diameter. Moreover, chronic allopurinol decreases LV weight and collagen density. Despite XO inhibition after acute and chronic allopurinol treatment, as both treatments reduce uric acid plasma levels, only acute allopurinol treatment reduces LV ROS determined using electron spin resonance spectroscopy. However, the CHF-enhanced myocardial thiobarbituric acid reactive substances levels were never modified. CONCLUSION: In experimental CHF, long-term allopurinol treatment, initiated in a pathological state of overt CHF, improves LV haemodynamics and function and prevents LV remodelling. These long-term effects are, at least partially, caused by a transient reduction of myocardial ROS shortly after initiation of allopurinol treatment, but whether other mechanism(s), independent of myocardial redox 'status', such as reduced inflammation, are implicated remains to be confirmed.

Allopurinol↗

PubMed2005

Pharmacological concentration of angiotensin-(1-7) activates NADPH oxidase after ischemia-reperfusion in rat heart through AT1 receptor stimulation.

The cardiovascular role of angiotensin-(1-7), especially in the functional and metabolic alterations associated with ischemia-reperfusion (IR), is still not clearly defined. Our objective was to evaluate the cardiac effects of angiotensin-(1-7), the receptors involved, and their relationships with NADPH oxidase activation under non-ischemic conditions and, during an ischemia-reperfusion sequence. Isolated perfused rat hearts underwent 45 min of non-ischemic perfusion, or 30 min of global ischemia followed by 30 min of reperfusion. Angiotensin-(1-7) and/or AT1 receptor blocker losartan or angiotensin-(1-7) receptor antagonist (D-Ala7)-angiotensin-(1-7) were perfused. Our results showed that angiotensin-(1-7) was without effect at low concentrations (10(-10) to 10(-7) M). At a pharmacological concentration, 0.5 microM angiotensin-(1-7) induced vasoconstriction, which was antagonised by losartan. After ischemia, we noted a partial recovery of functional parameters, which was not modified by any of the treatments. The expression of AT1 receptor mRNA was increased by ischemia-reperfusion, except in (D-Ala7)-angiotensin-(1-7) treated hearts. Angiotensin-(1-7) further increased the AT1 expression. NADPH oxidase activity was enhanced in 0.5 microM angiotensin-(1-7)-treated hearts subjected to ischemia-reperfusion, this effect was totally reversed by losartan. This is the first time that it has been shown that, in the heart, angiotensin-(1-7) at pharmacological concentration activates NADPH oxidase, an enzyme thought to be involved in several angiotensin II effects.

Angiotensin I↗

PubMed2003

Angiotensin II activates NADPH oxidase in isolated rat hearts subjected to ischaemia-reperfusion.

The role of angiotensin II in myocardial ischaemia-reperfusion is not clearly defined. In this respect, the involvement of NADPH oxidase remains to be determined. The aim of this study was 1) to evaluate the cardiac effects of angiotensin AT(1) receptor stimulation in non-ischaemic conditions of perfusion or during ischaemia-reperfusion, and 2) to measure the concomitant activation of NADPH oxidase in isolated rat hearts perfused with angiotensin II and/or Losartan. In non-ischaemic hearts, angiotensin II induced rapid and prolonged vasoconstrictive and negative inotropic effects. Ischaemia-reperfusion increased the mRNA expression of AT(1) and AT(2) receptors. During reperfusion, angiotensin II reduced the incidence of arrhythmias and the lactate dehydrogenase released, and increased NADPH oxidase mRNA expression and enzyme activity. Losartan co-administration totally antagonised the effects of angiotensin II. Our study demonstrates that ischaemia-reperfusion induces adaptative cardiac modifications, which allow exogenously added angiotensin II to stimulate myocardial NADPH oxidase through angiotensin AT(1) receptor activation.

Angiotensin II↗