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1.
Article in French | AIM (Africa) | ID: biblio-1264296

ABSTRACT

Le but de la présente étude était d'évaluer la prévalence des facteurs de risque cardiovasculaires conventionnels et leur association avec des facteurs socio-économiques dans une population traitée pour un syndrome coronarien aigu, au département de car¬diologie du CHU Ibn Rochd de Casablanca au Maroc. Méthode : L'étude a été réalisée chez 199 patients consécutifs au cours de la phase aiguë d'un syndrome coronarien aigu. Les critères d'inclusion étaient l'ad¬mission dans les 24 heures après le début de la dou¬leur thoracique. Le facteur de risque cardiovasculaire conventionnel le plus courant chez ces patients était essentiellement le tabagisme, suivi de l'hypertension artérielle et du diabète de type II. Résultats : La prévalence de l'hypertension et du diabète était plus élevée chez les femmes atteintes du syndrome coronarien aigu que chez les hommes. Cette différence s'est également maintenue après ajustement en fonction de l'âge. Une fréquence plus élevée d'individus avec un stress au travail faible et modéré que des individus présentant des niveaux de stress au travail élevés a été observée. Cependant, les femmes qui souffraient d'un syndrome corona¬rien aigu avaient un niveau de stress au travail plus élevé que les hommes. Cette différence statistique a disparu lorsque l'âge a été utilisé comme covariant. Il n'y avait pas de différence statistique dans l'acti¬vité physique liée au travail entre les hommes et les femmes. De plus, il n'y avait aucune association entre le niveau de stress au travail, l'activité physique liée au travail et les facteurs de risque cardiovasculaires conventionnels. Conclusion : Les facteurs de risque conventionnels les plus répandus chez les patients atteints du syn¬drome coronarien aigu inclus dans l'étude étaient le tabagisme actuel, le diabète et l'hypertension. Les femmes présentaient des niveaux de stress au travail plus élevés que les hommes. Cependant, les facteurs socioéconomiques n'étaient pas associés à la préva¬lence des facteurs de risque cardiovasculaires conven¬tionnels chez les hommes et les femmes


Subject(s)
Acute Coronary Syndrome , Cardiovascular System , Risk Factors , Senegal
2.
Arch Physiol Biochem ; 124(1): 54-60, 2018 Feb.
Article in English | MEDLINE | ID: mdl-28844165

ABSTRACT

CONTEXT: Heat generation by brown adipose tissue (BAT) in response to temperature reduction seems to be entirely related to sympathetic nervous stimulation. OBJECTIVE: To analyse if temperature reduction and norepinephrine may differently affect the expression of proteins related to energy metabolism in BAT. MATERIALS AND METHODS: Isolated rats BAT was incubated with/without norepinephrine (10-6 mol/L, 24 h at 32 °C and 37 °C). RESULTS: In BAT, 32 °C increased the protein expression levels of carnitine palmitoyltransferase-I and -II, mitochondrial uncoupling protein-1 (UCP-1) and the expression and activity of lactate dehydrogenase. Mitochondrial F1-ATP synthase α-chain expression was decreased at 32 °C compared to 37 °C. Norepinephrine and at 32 °C exposure, UCP-1 expression was increased but cytochrome-c oxidase and F1-ATP synthase α-chain expression was reduced with respect to 37 °C. DISCUSSION: Sympathetic stimulation seems not to be the only factor associated with heat generation. CONCLUSIONS: Temperature reduction by itself exerts some different effects on the expression of proteins related to the energy metabolism than norepinephrine.


Subject(s)
Adipose Tissue, Brown/metabolism , Energy Metabolism , Mitochondria/metabolism , Models, Biological , Norepinephrine/metabolism , Sympathetic Nervous System/metabolism , Thermogenesis , Adenosine Triphosphatases/metabolism , Adipose Tissue, Brown/enzymology , Adipose Tissue, Brown/innervation , Animals , Blotting, Western , Carnitine O-Palmitoyltransferase/metabolism , Cold Temperature , Electron Transport Complex IV/metabolism , In Vitro Techniques , Isoenzymes/metabolism , L-Lactate Dehydrogenase/metabolism , Male , Mitochondria/enzymology , Mitochondrial Proton-Translocating ATPases/metabolism , Oxidative Phosphorylation , Rats, Wistar , Uncoupling Protein 1/metabolism
3.
Rev. clín. esp. (Ed. impr.) ; 215(9): 486-494, dic. 2015. tab, ilus, graf
Article in English | IBECS | ID: ibc-146456

ABSTRACT

Introduction. Different alcoholic beverages exert different effects on inflammation and oxidative stress but these results are controversial and scanty in some aspects. We analyze the effect of different alcoholic beverages after a fat-enriched diet on lipid profile, inflammatory factors and oxidative stress in healthy people in a controlled environment. Methods. We have performed a cross-over design in five different weeks. Sixteen healthy volunteers have received the same oral fat-enriched diet (1486kcal/m2) and a daily total amount of 16g/m2 of alcohol, of different beverages (red wine, vodka, brandy or rum) and equivalent caloric intakes as sugar with water in the control group. We have measured the levels of serum lipids, high sensitivity C-reactive protein (hsCRP), tumor necrosis factor α (TNFα), interleukin 6 (IL-6), soluble phospholipase A2 (sPLA2), lipid peroxidation (LPO) and total antioxidant capacity (TAC). Results. Red wine intake was associated with decreased of mean concentrations of hsCRP, TNFα and IL-6 induced by fat-enriched diet (p<0.05); nevertheless, sPLA2 concentrations were not significantly modified. After a fat-enriched diet added with red wine, TAC increased as compared to the same diet supplemented with rum, brandy, vodka or the control (water with sugar) (p<0.05). Conclusions. Moderate red wine intake, but not other alcoholic beverages, decreased pro-inflammatory factors and increased total antioxidant capacity despite a fat-enriched diet intake in healthy young volunteers (AU)


Introducción. El efecto de las bebidas alcohólicas sobre la inflamación y el estrés oxidativo es variable y solo parcialmente conocido. Objetivo: analizar el efecto de diferentes bebidas alcohólicas sobre el perfil lipídico, factores de inflamación y estrés oxidativo en personas sanas con ingesta de una dieta enriquecida en grasas. Métodos. Se diseñó un estudio cruzado durante cinco semanas. Dieciséis voluntarios sanos recibieron la misma dieta enriquecida con grasa oral (1.486kcal/m2) más 16g/m2 de alcohol diarios, consumido como vino tinto, vodka, brandy o ron, o un equivalente calórico en el grupo control (azúcar y agua). Se midieron lípidos en suero, proteína C reactiva de alta sensibilidad (PCR-as), factor de necrosis tumoral (TNF) α, interleucina 6 (IL-6), fosfolipasa A2 soluble (sPLA2), la peroxidación lipídica (LPO) y la capacidad antioxidante total (TAC). Resultados. La ingesta de vino tinto se asoció con una disminución significativa de las concentraciones de PCR-as, TNFα e IL-6, inducida por una dieta rica en grasas (p <0,05). Las concentraciones de sPLA2 no se modificaron. El consumo de vino tinto, aún con una dieta rica en grasas, aumentó la capacidad antioxidante total comparada con el ron, brandy, vodka o el control (agua con azúcar) (p <0,05). Conclusiones. La ingesta moderada de vino tinto, pero no de otras bebidas alcohólicas, disminuyó las concentraciones de factores proinflamatorios y aumentó la capacidad antioxidante total, a pesar de la dieta enriquecida en grasa en voluntarios jóvenes sanos (AU)


Subject(s)
Adult , Female , Humans , Male , Alcohol Drinking/trends , Alcoholic Beverages , Oxidative Stress/physiology , Lipid Metabolism/physiology , Dietary Fats/therapeutic use , Inflammation/epidemiology , Antioxidants/therapeutic use , Wine , Cross-Over Studies , Lipoproteins/analysis , 28599 , Anthropometry/methods , Lipid Peroxidation/physiology
4.
Rev Clin Esp (Barc) ; 215(9): 486-94, 2015 Dec.
Article in English, Spanish | MEDLINE | ID: mdl-26297333

ABSTRACT

INTRODUCTION: Different alcoholic beverages exert different effects on inflammation and oxidative stress but these results are controversial and scanty in some aspects. We analyze the effect of different alcoholic beverages after a fat-enriched diet on lipid profile, inflammatory factors and oxidative stress in healthy people in a controlled environment. METHODS: We have performed a cross-over design in five different weeks. Sixteen healthy volunteers have received the same oral fat-enriched diet (1486kcal/m(2)) and a daily total amount of 16g/m(2) of alcohol, of different beverages (red wine, vodka, brandy or rum) and equivalent caloric intakes as sugar with water in the control group. We have measured the levels of serum lipids, high sensitivity C-reactive protein (hsCRP), tumor necrosis factor α (TNFα), interleukin 6 (IL-6), soluble phospholipase A2 (sPLA2), lipid peroxidation (LPO) and total antioxidant capacity (TAC). RESULTS: Red wine intake was associated with decreased of mean concentrations of hsCRP, TNFα and IL-6 induced by fat-enriched diet (p<0.05); nevertheless, sPLA2 concentrations were not significantly modified. After a fat-enriched diet added with red wine, TAC increased as compared to the same diet supplemented with rum, brandy, vodka or the control (water with sugar) (p<0.05). CONCLUSIONS: Moderate red wine intake, but not other alcoholic beverages, decreased pro-inflammatory factors and increased total antioxidant capacity despite a fat-enriched diet intake in healthy young volunteers.

5.
J Mol Endocrinol ; 54(2): 105-13, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25701828

ABSTRACT

It has been suggested that activated brown adipose tissue (BAT) shows increased glucose metabolic activity. However, less is known about metabolic activity of BAT under conditions of fasting and normal temperature. The aim of this study was to compare the possible differences in energetic metabolism between BAT and white adipose tissue (WAT) obtained from rabbits under the conditions of physiological temperature and 24 h after fasting conditions. The study was carried out on New Zealand rabbits (n=10) maintained for a period of 8 weeks at 23±2 °C. Food was removed 24 h before BAT and WAT were obtained. Protein expression levels of the glycolytic-related protein, glyceraldehyde-3-phosphate dehydrogenase, and pyruvate dehydrogenase were higher in WAT than that in BAT. The expression level of carnitine palmitoyltransferase 1 (CPT1) and CPT2, two fatty acid mitochondrial transporters, and the fatty acid ß-oxidation-related enzyme, acyl CoA dehydrogenase, was higher in BAT than in WAT. Cytosolic malate dehydrogenase expression and malate dehydrogenase activity were higher in WAT than in BAT. However, lactate dehydrogenase expression and lactate content were significantly higher in BAT than in WAT. In summary, this study for the first time, to our knowledge, has described how under fasting and normal temperature conditions rabbit BAT seems to use anaerobic metabolism to provide energetic fuel, as opposed to WAT, where the malate-aspartate shuttle and, therefore, the gluconeogenic pathway seem to be potentiated.


Subject(s)
Adipose Tissue, Brown/metabolism , Adipose Tissue, White/metabolism , Fasting , Temperature , Aconitate Hydratase/metabolism , Adipose Tissue, Brown/enzymology , Adipose Tissue, White/enzymology , Animals , Blotting, Western , Fatty Acids/metabolism , Glucose/metabolism , Glycolysis , L-Lactate Dehydrogenase/metabolism , Lactic Acid/metabolism , Lipid Metabolism , Malate Dehydrogenase/metabolism , Mitochondrial Proteins/metabolism , Rabbits
6.
Nutr Metab Cardiovasc Dis ; 23(11): 1107-14, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23434394

ABSTRACT

BACKGROUND AND AIM: To investigate whether rosuvastatin can improve insulin sensitivity in overweight rats having a high fat diet (HFD). The potential mechanisms involved in this action were evaluated, including SIRT-1, other factors involved in glucose metabolism and stress signaling pathways. METHODS AND RESULTS: Male Wistar rats (n = 30) were divided into three groups: (i) rats fed a standard diet (3.5% fat); (ii) rats fed a HFD (33.5% fat); and (iii) rats fed a HFD and treated with rosuvastatin (15 mg/kg/day). Evolution: 7 weeks. HFD rats showed increased body, epididymal and lumbar adipose tissue weights. Plasma levels of cholesterol, triglycerides, VLDL, glucose and insulin and leptin/adiponectin ratio were higher in HFD rats, and rosuvastatin treatment reduced them. SIRT-1, p53, PGC-1α, PPAR-γ and GLUT-4 protein levels in white adipose tissue (WAT) were lower, and JNK was higher in HFD rats compared to controls. Rosuvastatin treatment normalized expression of these mediators. Endothelium-dependent relaxation was reduced in mesenteric rings from HFD rats compared to controls and rosuvastatin enhanced it in HFD rats. CONCLUSION: Rosuvastatin treatment reduced insulin resistance without affecting body weight or WAT loss in HFD rats. Reduction of leptin and JNK, and enhancement of SIRT-1, p53, PGC-1α, PPAR-γ and GLUT-4 expression in WAT could contribute to insulin sensitization. Normalization of SIRT-1 expression in WAT could be considered a key novel mechanism that aids in explaining the beneficial effects of rosuvastatin on the amelioration of glucose metabolism and the arrangement of multiple signaling pathways participating in insulin resistance in overweight HFD rats.


Subject(s)
Adipose Tissue, White/drug effects , Fluorobenzenes/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hyperlipidemias/prevention & control , Insulin Resistance , Overweight/physiopathology , Pyrimidines/therapeutic use , Sirtuin 1/metabolism , Sulfonamides/therapeutic use , Adipokines/blood , Adipokines/metabolism , Adipose Tissue, White/immunology , Adipose Tissue, White/metabolism , Animals , Diet, High-Fat/adverse effects , Down-Regulation/drug effects , Endothelium, Vascular/drug effects , Endothelium, Vascular/physiopathology , Glucose Transporter Type 4/metabolism , Hyperlipidemias/etiology , MAP Kinase Signaling System/drug effects , Male , Overweight/etiology , Overweight/immunology , Overweight/metabolism , PPAR gamma/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Rats , Rats, Wistar , Rosuvastatin Calcium , Transcription Factors/metabolism , Vasodilation/drug effects
7.
Exp Physiol ; 98(5): 999-1008, 2013 May.
Article in English | MEDLINE | ID: mdl-23335007

ABSTRACT

Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) is emerging as a novel factor that plays a critical role in integrating signalling pathways in the control of cellular and systemic metabolism. We investigated the role of vascular expression of PGC-1α and related factors, such as sirtuin 1 (SIRT1), peroxisome proliferator-activated receptor γ (PPARγ) and adiponectin, during the atherosclerotic process. Endothelial function, vascular superoxide anion production and inflammatory mediators were also evaluated. This study was carried out in male New Zealand rabbits fed a diet containing 0.5% cholesterol and 14% coconut oil for 8 weeks. Animals developed mixed dyslipidaemia and atherosclerotic lesions, which were associated with endothelial dysfunction, aortic overproduction of superoxide anions and inflammation. Expression of PGC-1α, SIRT1, PPARγ and adiponectin was reduced (P<0.05) in aorta from atherosclerotic rabbits. Levels of PGC-1α were correlated negatively (P<0.05) with total cholesterol levels, aortic superoxide anion production and tumour necrosis factor-α expression, and positively (P<0.05) with maximal relaxation in response to acetylcholine. The observed results suggest that PGC-1α could be considered to be a link between the main atherosclerotic processes (endothelial dysfunction, oxidation and inflammation) and alterations of other factors involved in vascular wall integrity, such as SIRT1, PPARγ and adiponectin.


Subject(s)
Atherosclerosis/physiopathology , Transcription Factors/metabolism , Adiponectin/biosynthesis , Animals , Aorta/metabolism , Atherosclerosis/chemically induced , Atherosclerosis/pathology , CD36 Antigens/biosynthesis , Cholesterol, Dietary , Coconut Oil , Endothelium, Vascular/drug effects , Lipids/blood , Male , PPAR gamma/biosynthesis , Plant Oils , Rabbits , Sirtuin 1/biosynthesis , Vascular Cell Adhesion Molecule-1/biosynthesis , Vasodilation
8.
J Physiol Pharmacol ; 62(1): 87-94, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21451213

ABSTRACT

UNLABELLED: Several factors, including mineralocorticoids, have been implicated in the renal damage associated with hypertension. Peroxisome proliferator activated receptor gamma (PPAR-γ) agonists improve renal damage associated with different pathologies. Therefore, our hypothesis was that mineralocorticoid receptor blockade ameliorates renal damage associated with hypertension and that this improvement may be mediated by PPAR-γ. Spontaneously hypertensive rats (SHR) were treated with either vehicle or eplerenone, a mineralocorticoid receptor antagonist, at two different doses: 30 and 100 mg/kg/day for 10 weeks. Age-matched Wistar Kyoto rats (WKY) were used as a normotensive reference group. SHR showed tubulointersticial fibrosis and mild tubular atrophy. These alterations were accompanied by increases in renal cortex gene expression of transforming growth factor beta (TGF-ß) connective tissue growth factor (CTGF) and phosphorylated Smad2 protein levels, factors involved in the fibrotic response. Interleukin 1-beta (IL-1ß) and tumor necrosis factor alpha (TNF-α) gene expression were also increased. By contrast, lysyl oxidase (LOX) expression and PPAR-γ protein levels were decreased in SHR as compared with normotensive animals. Only the high dose of eplerenone was able to reduce blood pressure and partially prevent LOX down-regulation in SHR. Both eplerenone doses significantly ameliorated interstitial fibrosis and tubular atrophy, reduced TGF-ß, CTGF and cytokine gene expression, and decreased Smad2 activation, while normalizing PPAR-γ protein levels. CONCLUSIONS: Mineralocorticoid receptor activation participates in hypertension-associated renal damage. This effect seems to involve stimulation of both fibrotic and inflammatory processes mediated (at least in part) by a down-regulation of PPAR-γ that can favour an up-regulation of the TGF-ß/Smad signalling pathway.


Subject(s)
Hypertension/drug therapy , Hypertension/metabolism , Kidney Diseases/drug therapy , Kidney Diseases/metabolism , PPAR gamma/metabolism , Spironolactone/analogs & derivatives , Animals , Blood Pressure/drug effects , Connective Tissue Growth Factor/genetics , Connective Tissue Growth Factor/metabolism , Cytokines/genetics , Down-Regulation , Eplerenone , Gene Expression , Hypertension/genetics , Hypertension/physiopathology , Kidney Cortex/metabolism , Kidney Cortex/physiopathology , Kidney Diseases/genetics , Kidney Diseases/physiopathology , Male , Mineralocorticoid Receptor Antagonists , PPAR gamma/agonists , PPAR gamma/genetics , Protein-Lysine 6-Oxidase/genetics , Protein-Lysine 6-Oxidase/metabolism , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Receptors, Mineralocorticoid/metabolism , Signal Transduction , Smad2 Protein/metabolism , Spironolactone/pharmacology , Up-Regulation
9.
Hipertens. riesgo vasc ; 26(4): 138-144, jul.-ago. 2009. tab, graf
Article in Spanish | IBECS | ID: ibc-117992

ABSTRACT

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)


Subject(s)
Animals , Rats , Aldosterone/pharmacokinetics , Endothelium, Vascular , Inflammation/physiopathology , Hypertension/drug therapy , Mineralocorticoid Receptor Antagonists/pharmacokinetics , Inflammation Mediators/pharmacokinetics , Oxidative Stress , Nitric Oxide Synthase/pharmacokinetics , Cytokines/pharmacokinetics
11.
ScientificWorldJournal ; 6: 413-24, 2006 Apr 03.
Article in English | MEDLINE | ID: mdl-16604252

ABSTRACT

Aldosterone not only contributes to salt and water homeostasis, but also exerts direct cardiovascular and renal effects. Numerous experimental and clinical studies indicate that aldosterone participate in cardiac alterations associated with hypertension, heart failure, diabetes and other pathological entities. It is important to mention that dietary salt is a key factor in aldosterone-mediated cardiovascular damage, since damage was more evident in animals on a high-salt diet than animals on a low salt diet. A pathophysiological action of aldosterone involves development of extracellular matrix and fibrosis, inflammation, stimulation of reactive oxygen species production, endothelial dysfunction, cell growth and proliferation. Many studies showed local extra-adrenal production of aldosterone in brain blood vessel, and the heart, which contribute in an important manner to the pathological actions of this mineralocorticoid. Several studies such as RALES, EPHESUS, 4E and others, recently showed that mineralocorticoid-receptor (MR) antagonists, alone or in combination with ACE inhibitors or ARBs, reduced the risk of progressive target organ damage and hospitalization in patients with hypertension and heart failure. These clinical benefits support the therapeutic usefulness of MR antagonists.


Subject(s)
Aldosterone/physiology , Cardiovascular Physiological Phenomena , Kidney/physiology , Mineralocorticoid Receptor Antagonists/pharmacology , Receptors, Mineralocorticoid/physiology , Heart Diseases/physiopathology , Humans , Kidney Diseases/physiopathology
12.
Biogerontology ; 6(1): 49-60, 2005.
Article in English | MEDLINE | ID: mdl-15834663

ABSTRACT

UNLABELLED: Aging and estrogen-deprivation induce deleterious effects on body composition and vascular function in females. On the other hand, growth hormone (GH), whose production is reduced by age, exerts several vascular effects. The aim of this study was to investigate the effect of long-term estrogen deprivation and GH administration on body composition, vascular function and structure in aged female rats. METHODS: Twelve female Wistar rats were ovariectomized at 10 months of age. At 20 months of age, half of the ovariectomized rats were treated with GH for 4 weeks. The remaining ovariectomized rats animals and one group of six intact females were used as control groups. After the treatment period, animals were sacrificed and Specific Gravity Index (SGI) and periuterine fat weigh, as well as vascular reactivity and morphometry in aortic rings, were studied. RESULTS: No significant differences were found in SGI and periuterine fat weigh between ovariectomized and intact control rats. SGI was significantly increased by GH, and periuterine fat was reduced by the treatment. Dose-dependent relaxing responses to acetylcholine and isoproterenol were significantly diminished in ovariectomized rats as compared with intact animals, and GH treatment improved these responses. Ovariectomized animals showed significantly higher contracting responses to phenylephrine, acetylcholine + L-NAME and angiotensin-I than intact rats, and treatment with GH reduced them significantly. Media cross-sectional area was increased in ovariectomized rats as compared to intact animals, and GH reduced this area, but differences did not reach significance. CONCLUSION: GH has beneficial effects in body composition and endothelial function in old ovariectomized female rats.


Subject(s)
Aging/physiology , Human Growth Hormone/pharmacology , Postmenopause/physiology , Acetylcholine/pharmacology , Animals , Aorta, Thoracic/anatomy & histology , Aorta, Thoracic/drug effects , Aorta, Thoracic/physiology , Body Composition/drug effects , Dose-Response Relationship, Drug , Estrogens/deficiency , Female , Human Growth Hormone/physiology , Ovariectomy , Phenylephrine/pharmacology , Rats , Rats, Wistar , Recombinant Proteins/pharmacology , Vasoconstriction , Vasoconstrictor Agents/pharmacology , Vasodilation , Vasodilator Agents/pharmacology
16.
Exp Gerontol ; 38(9): 971-9, 2003 Sep.
Article in English | MEDLINE | ID: mdl-12954484

ABSTRACT

Aging is associated with alterations in cardiovascular system and changes in body composition. The aim of this study was to investigate the effect of GH on body composition, vascular function and structure in old female rats. Old (20 months) and adult (4 months) female Wistar rats were used. One group of old animals was treated with GH (2 mg/kg/day) for four weeks. Periuterine fat weight, specific gravity index (SGI), dose response to Acetylcholine, Isoprenaline, Phenylephrine and Acetylcholine in the presence of L-NAME and vascular morphology in aortic rings, were studied. Old rats showed increased fat weight and decreased SGI (p<0.05) as compared to adult animals. GH reduced fat weight (p<0.05) and tended to increase SGI (NS). Old rats showed impaired vasodilatation to Acetylcholine and Isoprenaline (p<0.05), and GH improved these responses (p<0.05). Contraction response to Phenylephrine was higher in old than in adults rats (p<0.05), but GH did not show any effect. Contraction induced by Acetylcholine+L-NAME was higher in old rats than in adults, and GH tended to reduce this response, although not significantly. Aortic media area was increased in old rats, and GH reduced this parameter (p<0.05). In conclusion, GH shows beneficial effects on body composition, vascular function and morphology in old female rats.


Subject(s)
Aging/physiology , Body Composition/drug effects , Growth Hormone/pharmacology , Vasodilation/drug effects , Adipose Tissue/anatomy & histology , Aging/pathology , Animals , Aorta, Thoracic/anatomy & histology , Aorta, Thoracic/drug effects , Aorta, Thoracic/physiology , Culture Techniques , Dose-Response Relationship, Drug , Female , Insulin-Like Growth Factor I/metabolism , Rats , Rats, Wistar , Specific Gravity/drug effects , Vasoconstriction/drug effects , Vasoconstrictor Agents/pharmacology , Vasodilator Agents/pharmacology
19.
J Hypertens ; 19(3 Pt 2): 539-45, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11327627

ABSTRACT

OBJECTIVES: To evaluate the relative participation of nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF) and prostanoids in the relaxing responses induced by acetylcholine and isoproterenol in isolated coronary arteries from adult Wistar- Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). DESIGN AND METHODS: Male adult WKY rats and SHR were used in the study. Segments from left coronary arteries (approximately 350-380 microm internal diameter and 2 mm long) were mounted in an isometric myograph and pre-contracted with serotonin. Dose-response curves to acetylcholine and isoproterenol were carried out in absence and presence of the NO synthesis inhibitor NG-nitro-L-arginine methyl ester (LNAME), the inhibitor of the cyclo-oxygenase, indomethacin and KCI. Areas under the respective dose-response curves were used to calculate the approximate relative participation of NO, EDHF and prostanoids. RESULTS: Relaxations to either acetylcholine or isoproterenol were lower in SHR than in WKY rats. In WKY rats, presence of LNAME diminished (P< 0.05) relaxation to acetylcholine from 10(-9) to 10(-6) mol/l, and induced a contracting response at 10(-5) and 10(-4) mol/l of acetylcholine. Addition of indomethacin did not significantly affect dose-related relaxation to acetylcholine 10(-9) to 10(-6) mol/l in WKY rats, and reduced (P < 0.05) the contracting response observed at 10(-5) mol/l of acetylcholine. In SHR, addition of LNAME markedly reduced (P< 0.05) acetylcholine relaxations, but did not produce any contracting effect. Addition of indomethacin on top of LNAME slightly (P< 0.05) enhanced relaxing response to acetylcholine in SHR. Presence of LNAME in the media diminished (P < 0.05) relaxation to isoproterenol in both WKY rats and SHR. Addition of indomethacin on top of LNAME increased (P< 0.05) isoproterenol-relaxing response to levels similar to and higher than control conditions in WKY rats and SHR, respectively. Addition of KCI blunted both acetylcholine- and isoproterenol-relaxations in both groups. CONCLUSIONS: NO and EDHF are the main endothelium-derived relaxing factors underlying acetylcholine and isoproterenol relaxations in rat coronary arteries, respectively. EDHF reduction, and not only NO reduction play a key role in the diminished coronary relaxations induced by acetylcholine and isoproterenol in SHR. An arachidonic acid derivative with contracting activity released by acetylcholine and isoproterenol in a differential manner, could oppose the relaxing actions of NO and EDHF.


Subject(s)
Biological Factors/physiology , Coronary Vessels/physiopathology , Hypertension/physiopathology , Vasodilation , Acetylcholine/pharmacology , Animals , Coronary Vessels/drug effects , Dose-Response Relationship, Drug , Enzyme Inhibitors/pharmacology , Isoproterenol/pharmacology , Male , NG-Nitroarginine Methyl Ester/pharmacology , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Vasoconstriction , Vasodilator Agents/pharmacology
20.
Nephrol Dial Transplant ; 16 Suppl 1: 40-4, 2001.
Article in English | MEDLINE | ID: mdl-11369819

ABSTRACT

BACKGROUND: Numerous studies have shown that elevated plasma cholesterol can exacerbate renal disease. However, the effect of lipids on renal structure and vascular function in normal kidneys is less well established. Therefore, the aim of this study was to evaluate the impact of hypercholesterolaemia on glomerular structure and vascular reactivity of segmental arteries in rabbits. In addition, we also studied whether or not atorvastatin can prevent these structural and vascular alterations in hypercholesterolaemic rabbits. METHODS: Male New Zealand rabbits were fed either a normal rabbit chow or a diet containing 1% cholesterol and treated or not with atorvastatin (1 mg/kg/day) for 12 weeks. Dose-response curves to acetylcholine (10(-9)-10(-4) mol/l) and sodium nitroprusside (10(-9)-10(-4) mol/l) were studied in segmental arteries in the presence or absence of the thromboxane A2/PGH2 receptor antagonist ifetroban (10(-5) mol/l). Glomerular size and structure were also evaluated. RESULTS: Compared with control animals, hypercholesterolaemic rabbits presented glomerular hypertrophy and several types of injuries (capillary collapse, hyalinosis and alterations of Bowman's capsule), suggesting diffuse glomerulosclerosis. Segmental arteries also showed relaxing responses to acetylcholine and sodium nitroprusside which were lower than and similar to, respectively, those of control animals. The presence of ifetroban improved the acetylcholine response only in hypercholesterolaemic rabbits. Atorvastatin treatment prevented vascular and most glomerular changes associated with hypercholesterolaemia even in the presence of very high cholesterol levels. CONCLUSIONS: Atorvastatin exerts a protective effect on renal damage associated with hypercholesterolaemia even in the presence of deleterious levels of plasma cholesterol.


Subject(s)
Anticholesteremic Agents/therapeutic use , Endothelium, Vascular/drug effects , Glomerulosclerosis, Focal Segmental/prevention & control , Heptanoic Acids/therapeutic use , Hypercholesterolemia/complications , Hypercholesterolemia/drug therapy , Pyrroles/therapeutic use , Renal Circulation/drug effects , Acetylcholine/pharmacology , Animals , Atorvastatin , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Cholesterol, Dietary , Disease Models, Animal , Endothelium, Vascular/physiology , Endothelium, Vascular/physiopathology , Kidney/drug effects , Kidney/pathology , Male , Nitroprusside/pharmacology , Oxazoles/pharmacology , Phenylephrine/pharmacology , Platelet Aggregation Inhibitors/pharmacology , Rabbits , Renal Circulation/physiology , Vasodilation/drug effects , Vasodilation/physiology
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