RESUMEN
In the view of the relationships between excessive sodium intake, immunity and target organ damage, we hypothesized that reduction in dietary sodium would be beneficial in the prevention of cardiac alterations through a restrained local immunity response in a rat model of metabolic syndrome. Sprague-Dawley rats were fed a 60% fructose diet with either a normal sodium (0.64% NaCl) or a low sodium content (<0.01% NaCl) for 8weeks. After 4weeks, rats were infused or not with angiotensin II (200ng·kg-1·min-1, sc) for 4weeks. Tail-cuff blood pressure was determined in conscious rats. Heart and left ventricle weight, cardiomyocyte size, and cardiac fibrosis were evaluated. We performed a transcriptomic analysis in order to identify differentially regulated cardiac mRNAs between normal and low sodium diets. We validated those results using qPCR and immunohistochemistry. Angiotensin II-induced blood pressure rise was blunted (~50%) in the low-sodium fed rats while cardiac hypertrophy and fibrosis were prevented. Transcriptomic analysis revealed 66 differentially regulated genes including 13 downregulated genes under the low sodium diet and implicated in the innate immune response. This was confirmed by reduced cardiac macrophages infiltration under the low sodium diet. Dietary sodium restriction prevents structural alterations of the heart of rats with fructose-induced insulin resistance and angiotensin II-hypertension. The reduction of cardiac inflammation and macrophage infiltration suggests that innate immunity has an important role in the beneficial effect of sodium restriction on cardiac remodeling.
Asunto(s)
Cardiomegalia , Dieta Hiposódica , Carbohidratos de la Dieta/efectos adversos , Fructosa/efectos adversos , Inmunidad Innata , Síndrome Metabólico , Animales , Cardiomegalia/dietoterapia , Cardiomegalia/inmunología , Carbohidratos de la Dieta/farmacología , Modelos Animales de Enfermedad , Fibrosis , Fructosa/farmacología , Síndrome Metabólico/inducido químicamente , Síndrome Metabólico/dietoterapia , Síndrome Metabólico/inmunología , Ratas , Ratas Sprague-Dawley , Cloruro de Sodio Dietético/efectos adversos , Cloruro de Sodio Dietético/farmacologíaRESUMEN
We assessed the influence of SODB, a melon superoxide dismutase (SOD), on left ventricular (LV) hypertrophy in SHR. SODB (4 or 40U SOD) was given orally for 4 or 28 days to SHR. For each treatment period, LV weight index (LVWI) and cardiomyocytes size were measured. SOD, glutathione peroxidase (GPx) and catalase expressions, and LV production and presence of superoxide anion were determined. Pro-inflammatory markers were also measured. SODB reduced LVWI and cardiomyocytes size after 4 or 28 days. Cardiac SOD and GPx increased by 30-40% with SODB. The presence but not production of superoxide anion was significantly reduced by SODB. No effect of SODB was detected on inflammatory status in any group. The beneficial effect of SODB on cardiac hypertrophy seems to be related to the stimulation of endogenous antioxidant defense, suggesting that SODB may be of interest as a dietary supplementation during conventional antihypertensive therapy.
Asunto(s)
Antioxidantes/metabolismo , Cardiomegalia/tratamiento farmacológico , Cucurbitaceae/enzimología , Superóxido Dismutasa/metabolismo , Animales , Antihipertensivos/farmacología , Presión Sanguínea/efectos de los fármacos , Catalasa/metabolismo , Glutatión Peroxidasa/metabolismo , Hipertensión/tratamiento farmacológico , Hipertensión/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Endogámicas SHR , Superóxido Dismutasa/farmacología , Superóxidos/metabolismoRESUMEN
BACKGROUND/AIM: In chronic renal failure the increase in cardiovascular risk is in part related to the high prevalence of left ventricular hypertrophy. The aim of the present monocentric retrospective study was to evaluate the influence of the presence of parenchymal kidney disease on left ventricular geometry in normotensive (arterial pressure <140/90 mm Hg) patients (KD+, n = 50, mean age 39 ± 19 years) with mild to moderate renal failure (stage 2-3 chronic kidney disease). METHODS: Left ventricular geometry was estimated by echocardiography and compared to a group of healthy subjects with similarly reduced renal function as a consequence of renal donation (KD-, n = 63, mean age 52 ± 12 years). RESULTS: Subjects with and without kidney disease had similar blood pressure, body mass index and isotopic glomerular filtration rate. Left ventricular mass (LVM) indexed to body surface area was greater in KD+ as compared to KD- subjects and the difference was more pronounced in women than in men. The increase in LVM in KD+ patients was associated with lower albuminemia and hematocrit, and a higher plasma renin activity and aldosterone as compared to KD- subjects. In multivariate analysis, kidney disease emerged as an important determinant of LVM index independently of age, gender and blood pressure. CONCLUSION: This observation suggests that the presence of kidney disease has an independent amplifying effect on LVM which could be related to volume overload and/or prohypertrophic factors such as aldosterone.
Asunto(s)
Corazón/fisiopatología , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/fisiopatología , Adolescente , Adulto , Anciano , Aldosterona/metabolismo , Presión Sanguínea , Índice de Masa Corporal , Enfermedades Cardiovasculares/complicaciones , Ecocardiografía , Femenino , Tasa de Filtración Glomerular , Ventrículos Cardíacos , Humanos , Masculino , Persona de Mediana Edad , Nefrectomía , Estudios Retrospectivos , Donantes de Tejidos , Función Ventricular Izquierda/fisiología , Adulto JovenRESUMEN
Sodium depletion has a protective effect on target-organ damage in hypertension independent of blood pressure. Here we tested whether chronic dietary sodium restriction may prevent the development of renal alterations associated with insulin resistance by reducing the inflammatory and oxidant state. Rats were fed normal-salt-60% fructose, low-salt-60% fructose, or control normal-salt diet for 12 weeks. Insulin resistance induced by high-fructose diet was associated with an increase in albuminuria, tubular and glomerular hypertrophy, and inflammation of kidney and adipose tissue. The low-salt diet improved insulin sensitivity and prevented kidney damage. These beneficial effects of sodium depletion were associated with a decrease in renal inflammation (macrophage infiltration, IL-6, TNF-α) and oxidative stress (NADPH oxidase activity), and a prevention of histologic changes in retroperitoneal fat induced by high fructose. Thus, dietary salt depletion has beneficial effects on renal and metabolic alterations associated with a high-fructose diet in rats.
Asunto(s)
Albuminuria/prevención & control , Dieta Hiposódica , Fructosa , Resistencia a la Insulina , Riñón/metabolismo , Albuminuria/sangre , Albuminuria/inducido químicamente , Albuminuria/inmunología , Albuminuria/patología , Animales , Glucemia/metabolismo , Desmina/metabolismo , Modelos Animales de Enfermedad , Fibrosis , Mediadores de Inflamación/metabolismo , Interleucina-6/metabolismo , Grasa Intraabdominal/metabolismo , Grasa Intraabdominal/patología , Riñón/inmunología , Riñón/ultraestructura , Macrófagos/inmunología , Masculino , NADPH Oxidasas/metabolismo , Estrés Oxidativo , Ratas , Ratas Sprague-Dawley , Factores de Tiempo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVE: L-Thyroxine-suppressive therapy benefits high-risk differentiated thyroid cancer patients by decreasing recurrence rates and cancer-related mortality. However, fully suppressed serum thyroid-stimulating hormone (TSH) implies a state of subclinical hyperthyroidism (SCH) with associated adverse cardiac effects. Because left ventricular (LV) diastolic dysfunction may be the first manifestation of more severe LV failure, and to balance the risks from thyroid cancer recurrence with risks of cardiac failure, the purpose of this study was to analyse new parameters of LV function in asymptomatic patients with exogenous SCH. DESIGN: Case-control study with 24 patients on TSH-suppressive therapy of short duration (≤ 4 years) after thyroid ablative therapy for differentiated thyroid carcinoma and 20 age- and sex-matched subjects. MEASUREMENTS: LV function [LV global strain and strain rate (SR) curves] was assessed by speckle tracking imaging echocardiography in each subject. RESULTS: Patients and controls do not differ in body mass index, systolic blood pressure and heart rate. No significant differences were observed in LV morphology (LV mass and relative wall thickness), cardiac output and parameters of LV systolic function between patients on suppressive therapy and controls. When compared with controls, patients with exogenous SCH had a significantly impaired longitudinal protodiastolic strain, SR and strain diastolic index but preserved radial strain and SR function. CONCLUSIONS: In subjects with SCH at the early phase of TSH-suppressive therapy, evidence of isolated longitudinal LV diastolic dysfunction was observed, despite a normal LV morphology. Further prospective studies to clarify the prognosis of picking-up early diastolic dysfunction in asymptomatic patients are needed before serial measurements could be recommended.
Asunto(s)
Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/fisiopatología , Tirotropina/sangre , Tiroxina/efectos adversos , Tiroxina/uso terapéutico , Disfunción Ventricular Izquierda/inducido químicamente , Adulto , Anciano , Estudios de Casos y Controles , Ecocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Tiroides/sangreRESUMEN
BACKGROUND: Rats fed an early and long-term high-salt diet (HS, NaCl 8%) developed significant cardiovascular hypertrophy without major changes in blood pressure. The mechanism of this cardiac hypertrophy has not been yet elucidated. METHODS: In the present work, we assessed the influence of volume overload and arterial stiffness on the structural and functional cardiac changes induced by a high salt feeding from weaning to 5 months of age in Sprague-Dawley rats. RESULTS: Cardiac hypertrophy in HS rats was associated with clear augmentation in the size of left ventricular (LV) cardiomyocyte as compared with rats fed regular diet (NS). Echocardiography revealed a marked increase in relative wall thickness. Of note, no alteration of global and regional systolic and diastolic function was detected in HS rats. High sodium consumption was associated with a slight increase in aortic mean and pulse pressure (PP) without effect on pulse wave velocity (PWV) and elastic modulus. Plasma volume and central venous pressure were higher in HS than NS rats. Whereas plasma endothelin level was twofold higher in HS than in NS rats, LV endothelin level was similar in both groups. Treatment by the endothelin receptors blocker bosentan had no detectable effect on the changes induced by HS diet. CONCLUSIONS: High sodium intake was associated with concentric cardiac hypertrophy without change of systolic and diastolic function. Aortic rigidity was not a determinant of cardiac hypertrophy. Beside a likely direct effect of sodium on cardiovascular system the slight increase in arterial pressure and plasma volume play a role.
Asunto(s)
Cardiomegalia/etiología , Volumen Plasmático/efectos de los fármacos , Cloruro de Sodio Dietético/administración & dosificación , Resistencia Vascular/efectos de los fármacos , Animales , Aorta Torácica/efectos de los fármacos , Aorta Torácica/fisiología , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Bosentán , Cardiomegalia/patología , Cardiomegalia/fisiopatología , Ecocardiografía Doppler , Antagonistas de los Receptores de Endotelina , Endotelina-1/sangre , Masculino , Flujo Pulsátil/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Cloruro de Sodio Dietético/efectos adversos , Sulfonamidas/farmacologíaRESUMEN
1. Time course of renal alterations associated with long-term (since weaning) administration of a high sodium (HS, 8% NaCl) diet was assessed in Sprague-Dawley rats. Reversal by acute administration of the mineralocorticoid receptor antagonist, potassium canrenoate (40 mg/kg, i.p.) or the type 1 angiotensin II receptor antagonist, losartan (10 mg/kg, i.v.), was evaluated at the age of 5 months (i.e. after 21 weeks of HS feeding). 2. High sodium intake had no detectable effect on blood pressure; however, albuminuria was always higher in the HS than control group. Glomerular filtration rate, renal plasma flow and filtration fraction decreased significantly after 12 weeks of HS diet by approximately 50, 30 and 20%, respectively. Canrenoate was effective and markedly reversed the renal hypofiltration associated with HS feeding without change in systemic blood pressure. In contrast, losartan reduced blood pressure and it was devoid of a beneficial effect on renal function. 3. The present observations indicate that hypofiltration and hypoperfusion of the kidney occurred progressively and require a long period of exposure to a high sodium intake. Albuminuria, which increased before detectable changes in renal function, may represent an early marker of renal dysfunction. The beneficial effect of acute administration of potassium canrenoate favours the participation of aldosterone, at least partially, in the sustained deterioration of renal function after 21 weeks of high sodium feeding.
Asunto(s)
Ácido Canrenoico/uso terapéutico , Enfermedades Renales/inducido químicamente , Enfermedades Renales/tratamiento farmacológico , Sodio en la Dieta/efectos adversos , Albuminuria/inducido químicamente , Animales , Presión Sanguínea/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Tasa de Filtración Glomerular/efectos de los fármacos , Losartán/uso terapéutico , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
The ability of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor simvastatin to reverse established cardiovascular and renal alterations and oxidative stress was assessed in angiotensin II (AngII) hypertension. Sprague-Dawley rats infused with AngII (200 ng/kg per minute for 17 days) were concomitantly treated or not for the last 7 days with simvastatin, apocynin, tempol, and hydralazine (60, 60, 30, and 15 mg/kg per day, respectively). Only hydralazine lowered AngII hypertension. Simvastatin and apocynin lowered cardiac hypertrophy by 52% and 54% and reversed the marked rise in albuminuria by 25% and 70%. Neither tempol nor hydralazine affected cardiac mass or albuminuria. None of the treatments modified the AngII-induced increase in carotid media thickness. The rise in cardiac superoxide anion production (lucigenin-enhanced chemiluminescence method) induced by AngII was reversed by all treatments. Enhanced plasma concentration of advanced oxidation protein products (spectrophotometry using chloramine T) was unaffected by simvastatin and tempol, but it was reversed by apocynin and hydralazine. Our results indicate that simvastatin reverse established cardiac and renal alterations in AngII hypertension independently of arterial pressure. It is suggested that oxidative stress participates in the maintenance of target organ damage and that antioxidant properties are involved in the beneficial influence of the statin.
Asunto(s)
Antioxidantes/farmacología , Hipertensión/tratamiento farmacológico , Hipolipemiantes/farmacología , Estrés Oxidativo/efectos de los fármacos , Simvastatina/farmacología , Acetofenonas/farmacología , Albuminuria/inducido químicamente , Albuminuria/tratamiento farmacológico , Angiotensina II/farmacología , Animales , Antihipertensivos/farmacología , Cardiomegalia/inducido químicamente , Cardiomegalia/tratamiento farmacológico , Arterias Carótidas/efectos de los fármacos , Arterias Carótidas/fisiopatología , Óxidos N-Cíclicos/farmacología , Hidralazina/farmacología , Hipertensión/inducido químicamente , Hipertensión/fisiopatología , Masculino , Ratas , Ratas Sprague-Dawley , Marcadores de Spin , Superóxidos/metabolismo , Túnica Media/efectos de los fármacos , Túnica Media/fisiopatologíaRESUMEN
Reversal by the mineralocorticoid receptor antagonist spironolactone on cardiac and renal abnormalities, associated with long-term (since weaning) administration of a high (2 and 8% NaCl chow, HS2 and HS8) sodium diet, was assessed in Sprague-Dawley rats. At the age of 5 mo, spironolactone (20 or 100 mg/kg, gavage) or placebo were given for 14 days to HS2 and HS8 rats. A group fed a regular diet (0.8% NaCl, NS) remained untreated. High sodium intake had no detectable effect on blood pressure; however, cardiac mass index and cross-sectional area of the carotid artery, as well as albuminuria, were increased only in the HS8 group compared with the control group on NS diet. In addition, a marked reduction in glomerular filtration rate (by 40%), associated with a nonproportional fall in renal plasma flow (thus resulting in a decrease in filtration fraction), was observed only in the HS8 group. No change in cardiac and renal fibrosis was detected. Production of the reactive oxygen species (ROS) by aortic tissue was increased in HS8 rats, whereas ROS production by the heart was unaffected. Only the high dose of spironolactone was effective, as it markedly reversed the cardiac hypertrophy and renal hypofiltration associated with the HS8 feeding. The changes were observed in the absence of any effect on systemic blood pressure and production of ROS. These observations favor aldosterone's role in the deleterious effects of marked and prolonged increases in sodium intake.
Asunto(s)
Cardiomegalia/inducido químicamente , Cardiomegalia/prevención & control , Enfermedades Renales/inducido químicamente , Enfermedades Renales/prevención & control , Sodio en la Dieta/efectos adversos , Sodio/administración & dosificación , Sodio/efectos adversos , Espironolactona/administración & dosificación , Administración Oral , Animales , Presión Sanguínea/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Cardiomegalia/patología , Cardiomegalia/fisiopatología , Diuréticos/administración & dosificación , Interacciones Farmacológicas , Frecuencia Cardíaca/efectos de los fármacos , Enfermedades Renales/patología , Enfermedades Renales/fisiopatología , Masculino , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Sprague-DawleyRESUMEN
Angiotensin-converting enzyme inhibitors (ACE-Is) prevent target organ damage in several models of hypertension. The aim of this study was to assess the influence of the ACE-I enalapril (10 mg/kg(-1) per day, gavage) on the cardiovascular alterations and production of free radicals induced by chronic infusion of angiotensin II (Ang II, 200 ng/kg(-1) per minute, s.c.) in Sprague-Dawley rats. Enalapril was given concomitantly for the 10 days of Ang II infusion (prevention) or from day 10 to 17 of Ang II infusion (intervention). The influence of the NADPH oxidase inhibitor apocynin (600 mg/L(-1) in drinking water) was evaluated. Enalapril and apocynin had no effect on hypertension in the prevention and intervention studies. Enalapril prevented the increase in heart weight index (HWI), carotid cross-sectional area (CSA) and albuminuria induced by Ang II. Enalapril reduced HWI and albuminuria whereas CSA was not affected in the intervention study. Apocynin had effects comparable to enalapril. Both enalapril and apocynin reduced the overproduction of superoxide anion by the left ventricle and rise in advanced oxidation protein products induced by Ang II. Therefore, the antioxidant but not the antihypertensive effect of enalapril may participate in the prevention and treatment of the Ang II-induced cardiovascular and renal alterations.
Asunto(s)
Angiotensina II/fisiología , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Enalapril/uso terapéutico , Hipertensión/tratamiento farmacológico , Acetofenonas/uso terapéutico , Albuminuria/etiología , Angiotensina II/uso terapéutico , Animales , Antiinflamatorios no Esteroideos/uso terapéutico , Modelos Animales de Enfermedad , Hipertensión/prevención & control , Masculino , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismoRESUMEN
The influence of a low-sodium (LS) diet was assessed on the cardiac and renal alterations and pro-oxidant effect associated with a 10-day infusion of angiotensin II (200 or 400 ng. kg(-1). min(-1), osmotic pumps). Tail-cuff pressure (TCP), albuminuria, and renal blood flow were determined at the end of the experiments. Heart weight index (HWI) and production of superoxide anion (O(2)(-).) by the left ventricle and H(2)O(2) by the aorta was measured with the use of bioluminescence. Although the final TCP was similar in LS and normal sodium (NS) rats infused with high and low doses of angiotensin II, respectively, the increase in HWI was prevented by the LS diet. Sodium restriction reduced the rise in albuminuria without a change in the renal effect of angiotensin II. The increased production of O(2)(-). and H(2)O(2) observed in NS rats was abrogated in LS rats. The beneficial influence of dietary sodium restriction on target organ damage induced by angiotensin II is independent of arterial pressure reduction and possibly related to attenuation of the prooxidant effect of the peptide.