RESUMEN
BACKGROUND AND AIMS: Although many studies have reported the effects of AT1 receptor on dietary salt overload, the role of AT2 receptor in this model is far from completely elucidated. The present study aimed to better understand the role of AT2 receptor in cardiac structure alterations in response to chronic high salt intake in rats. METHODS AND RESULTS: Male Wistar rats were fed a normal or high salt diet from weaning until 18 weeks of age. Both groups were subdivided into two groups. Starting at 7 weeks of age, rats were treated with or without compound 21 (0.3 mg/kg/day, n = 16), an AT2 receptor agonist. Metabolics and structural parameters were measured. BP, transverse cardiomyocyte and intersticial fibrose was higher in animals fed with high salt diet compared with normal salt fed animals. CONCLUSION: Compound 21 prevented the development of cardiac hypertrophy and fibrosis, reduced the increase in blood pressure and prevented the lower weight gain in animals fed a high salt diet.
Asunto(s)
Cardiomegalia/prevención & control , Fármacos Cardiovasculares/farmacología , Miocitos Cardíacos/efectos de los fármacos , Receptor de Angiotensina Tipo 2/agonistas , Cloruro de Sodio Dietético , Sulfonamidas/farmacología , Tiofenos/farmacología , Remodelación Ventricular/efectos de los fármacos , Animales , Presión Sanguínea/efectos de los fármacos , Cardiomegalia/metabolismo , Cardiomegalia/patología , Cardiomegalia/fisiopatología , Modelos Animales de Enfermedad , Fibrosis , Hipertensión/metabolismo , Hipertensión/fisiopatología , Hipertensión/prevención & control , Masculino , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Ratas Wistar , Receptor de Angiotensina Tipo 2/metabolismo , Transducción de Señal , Aumento de Peso/efectos de los fármacosRESUMEN
This study aimed to evaluate the systemic and renal renin-angiotensin-aldosterone system (RAAS) at birth in male and female offspring and in mothers fed a high sodium diet (HSD) before and during gestation. Female Wistar rats were fed a HSD (8.0% NaCl) or a normal sodium diet (1.3% NaCl) from 8 weeks of age until delivery of their first litter. Maternal body weight, tail blood pressure, and food and water intake were evaluated. The litter sizes were assessed, and the body and kidney weights of the offspring were measured. Both mothers and offspring were euthanized immediately following the birth of the pups to evaluate plasma renin activity (PRA), renal renin content (RRC), renal angiotensin-converting enzyme (ACE) activity, renal angiotensin (Ang) II content, serum aldosterone (ALDO) levels, and renal cortical and medullary renin messenger RNA expression. In mothers in the HSD group, water intake and kidney mass were higher, whereas renal ACE activity, Ang II, PRA, ALDO and RRC were decreased. In the offspring of HSD-fed dams, the body and kidney mass were lower in both genders, renal ACE activity was lower in females and renal Ang II was lower in males. PRA, RRC, renin gene expression and ALDO levels did not differ between the groups of offspring. The data presented herein showed that a maternal HSD during pregnancy induces low birth weight and a sex-specific response in the RAAS in offspring.
RESUMEN
BACKGROUND AND AIM: To evaluate the effects of low or high salt intake during pregnancy on left ventricle of adult male offspring. METHODS AND RESULTS: Low- (LS, 0.15%), normal- (NS, 1.3%) or high-salt (HS, 8% NaCl) diet was given to Wistar rats during pregnancy. During lactation all dams received NS as well as the offspring after weaning. To evaluate cardiac response to salt overload, 50% of each offspring group was fed a high-salt (hs, 4% NaCl) diet from the 21st to the 36th week of age (LShs, NShs, HShs). The remaining 50% was maintained on NS (LSns, NSns and HSns). Echocardiography was done at 20 and 30 weeks of age. Mean blood pressure (MBP), histology and left ventricular angiotensin II content (AII) were analyzed at 36 weeks of age. Interventricular septum, left ventricular posterior wall and relative wall thickness increased from the 20th to the 30th week of age only in HShs, cardiomyocyte mean volume was higher in HShs compared to NShs, LShs and HSns. AII and left ventricular fibrosis were not different among groups. CONCLUSIONS: HS during pregnancy programs adult male offspring to a blood pressure and angiotensin II independent concentric left ventricular hypertrophy, with no fibrosis, in response to a chronic high-salt intake.
Asunto(s)
Miocardio/ultraestructura , Cloruro de Sodio Dietético/administración & dosificación , Cloruro de Sodio Dietético/efectos adversos , Angiotensina II/sangre , Animales , Presión Sanguínea/efectos de los fármacos , Ecocardiografía , Femenino , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/fisiopatología , Hipertrofia Ventricular Izquierda/etiología , Hipertrofia Ventricular Izquierda/fisiopatología , Masculino , Peptidil-Dipeptidasa A/genética , Peptidil-Dipeptidasa A/metabolismo , Potasio/sangre , Embarazo , Efectos Tardíos de la Exposición Prenatal/etiología , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Ratas , Ratas Wistar , Sistema Renina-Angiotensina/efectos de los fármacos , Sistema Renina-Angiotensina/genética , Sodio/sangre , Sodio/orinaRESUMEN
The present study was designed to evaluate, in Wistar rats, the effect of high- or low-salt diet on the hemodynamic parameters and on the renal and lumbar sympathetic nerve activity. The renal gene expression of the renin angiotensin system components was also evaluated, aiming to find some correlation between salt intake, sodium homeostasis and blood pressure increase. Male Wistar rats received low (0.06% Na, TD 92141-Harlan Teklad), a normal (0.5% Na, TD 92140), or a high-salt diet (3.12% Na, TD 92142) from weaning to adulthood. Hemodynamic parameters such as cardiac output and total peripheral resistance, and the renal and lumbar sympathetic nerve activity were determined (n=45). Plasma renin activity, plasma and renal content of angiotensin (ANG) I and II, and the renal mRNA expression of angiotensinogen, renin, AT1 and AT2 receptors were also measured (n=24). Compared to normal- and low-salt diet-, high-salt-treated rats were hypertensive and developed an increase (P<0.05) in total peripheral resistance and lumbar sympathetic nerve activity. A decrease in renal renin and angiotensinogen-mRNAs and in plasma ANG II and plasma renin activity was also found in salt overloaded animals. The renal sympathetic nerve activity was higher (P<0.05) in low- compared to high-salt-treated rats, and was associated with an increase (P<0.05) in renal ANG I and II and with a decrease (P<0.05) in AT2 renal mRNA. Plasma ANG I and II and plasma renin activity were higher in low- than in normal-salt rats. Our results show that increased blood pressure is associated with increases in lumbar sympathetic nerve activity and total peripheral resistance in high-salt-treated rats. However, in low-salt-treated rats an increase in the renal sympathetic nerve was correlated with an increase in the renal content of ANG I and II and with a decrease in AT2 renal mRNA. These changes are probably in favor of the antinatriuretic response and the sodium homeostasis in the low-salt group.
Asunto(s)
Angiotensinógeno/genética , Angiotensinas/genética , Cloruro de Sodio Dietético/farmacología , Sistema Nervioso Simpático/efectos de los fármacos , Angiotensina I/sangre , Angiotensina I/genética , Angiotensina I/metabolismo , Angiotensina II/sangre , Angiotensina II/genética , Angiotensina II/metabolismo , Angiotensinógeno/sangre , Angiotensinógeno/metabolismo , Angiotensinas/sangre , Angiotensinas/metabolismo , Animales , Regulación de la Expresión Génica/efectos de los fármacos , Hipertensión/inducido químicamente , Hipertensión/fisiopatología , Riñón/efectos de los fármacos , Riñón/inervación , Riñón/metabolismo , Masculino , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Renina/sangre , Renina/genética , Renina/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sistema Nervioso Simpático/fisiologíaRESUMEN
It has been suggested that iron overload may be carcinogenic. In the present study, we evaluated the effect of plasma and prostate carotenoid concentration on oxidative DNA damage in 12-week-old Wistar rats treated with intraperitoneal (ip) ferric nitrilotriacetate (Fe-NTA) (10 mg Fe/kg). Plasma beta-carotene and lycopene concentrations were measured as a function of time after ip injection of carotenoids (10 mg kg(-1) day(-1) beta-carotene or lycopene) in rats. The highest total plasma concentration was reached 3 and 6 h after ip injection of lycopene or beta-carotene, respectively. After 5 days of carotenoid treatment, lycopene and beta-carotene were present in the 0.10-0.51 nmol/g wet tissue range in the prostate. Using a sensitive method to detected 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) by HPLC/EC, the level of 8-oxodGuo in rat prostate DNA was significantly higher (6.3 +/- 0.6 residues/10(6) dGuo) 3 h after Fe-NTA injection compared with control rats (1.7 +/- 0.3 residues/10(6) dGuo). Rats supplemented with lycopene or beta-carotene for 5 days prior to Fe-NTA treatment showed a reduction of about 70% in 8-oxodGuo levels to almost control levels. Compared with control rats, the prostate of Fe-NTA-treated animals showed a 78% increase in malondialdehyde accumulation. Lycopene or beta-carotene pre-treatment almost completely prevented lipid damage. Epidemiological studies have suggested a lower risk of prostate cancer in men reporting a higher consumption of tomato products. However, before associating this effect with tomato sauce constituents, more information is required. The results described here may contribute to the understanding of the protective effects of carotenoids against iron-induced oxidative stress.
Asunto(s)
Antioxidantes/análisis , Carotenoides/sangre , Daño del ADN/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Próstata/efectos de los fármacos , beta Caroteno/sangre , 8-Hidroxi-2'-Desoxicoguanosina , Animales , Carcinógenos/farmacología , Carotenoides/análisis , Cromatografía Líquida de Alta Presión , ADN/química , ADN/efectos de los fármacos , Desoxiguanosina/análogos & derivados , Desoxiguanosina/análisis , Compuestos Férricos/farmacología , Licopeno , Masculino , Ácido Nitrilotriacético/análogos & derivados , Ácido Nitrilotriacético/farmacología , Próstata/química , Próstata/patología , Ratas , Ratas Wistar , beta Caroteno/análisisRESUMEN
It has been suggested that iron overload may be carcinogenic. In the present study, we evaluated the effect of plasma and prostate carotenoid concentration on oxidative DNA damage in 12-week-old Wistar rats treated with intraperitoneal (ip) ferric nitrilotriacetate (Fe-NTA) (10 mg Fe/kg). Plasma ß-carotene and lycopene concentrations were measured as a function of time after ip injection of carotenoids (10 mg kg-1 day-1 ß-carotene or lycopene) in rats. The highest total plasma concentration was reached 3 and 6 h after ip injection of lycopene or ß-carotene, respectively. After 5 days of carotenoid treatment, lycopene and ß-carotene were present in the 0.10-0.51 nmol/g wet tissue range in the prostate. Using a sensitive method to detected 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) by HPLC/EC, the level of 8-oxodGuo in rat prostate DNA was significantly higher (6.3 ± 0.6 residues/10(6) dGuo) 3 h after Fe-NTA injection compared with control rats (1.7 ± 0.3 residues/10(6) dGuo). Rats supplemented with lycopene or ß-carotene for 5 days prior to Fe-NTA treatment showed a reduction of about 70 percent in 8-oxodGuo levels to almost control levels. Compared with control rats, the prostate of Fe-NTA-treated animals showed a 78 percent increase in malondialdehyde accumulation. Lycopene or ß-carotene pre-treatment almost completely prevented lipid damage. Epidemiological studies have suggested a lower risk of prostate cancer in men reporting a higher consumption of tomato products. However, before associating this effect with tomato sauce constituents, more information is required. The results described here may contribute to the understanding of the protective effects of carotenoids against iron-induced oxidative stress.
Asunto(s)
Animales , Masculino , Ratas , Antioxidantes/análisis , Carotenoides/sangre , Daño del ADN/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Próstata/efectos de los fármacos , beta Caroteno/sangre , Cromatografía Líquida de Alta Presión , Carcinógenos/farmacología , Carotenoides/análisis , ADN , Desoxiguanosina/análisis , Desoxiguanosina/análogos & derivados , Compuestos Férricos/farmacología , Ácido Nitrilotriacético/análogos & derivados , Ácido Nitrilotriacético/farmacología , Próstata/química , Próstata/patología , Ratas Wistar , beta Caroteno/análisisRESUMEN
BACKGROUND AND AIM: To study the influence of high salt intake during pregnancy and lactation on body weight, blood pressure, and the function of the renin-angiotensin system in adult rats. METHODS AND RESULTS: Female Wistar rats received a low (0.15 NaCl), normal (1.30), or high (8% diet) salt diet. Mating occurred on the 12th week of age. From weaning, the offspring received normal salt diet. Weekly tail-cuff blood pressure and body weight measurements were performed during pregnancy and in the offspring (body weight since weaning and tail-cuff blood pressure between the 8th and the 12th week of age). Salt sensitivity of the blood pressure was evaluated and plasma renin activity determinations were performed in the 12-week-old offspring. Immunohistochemistry for renal angiotensin II was performed in the adult offspring. Renal mass and the number of glomeruli were determined. Tail-cuff blood pressure was higher in salt overloaded dams than in normal and low salt ones. In the adult offspring from the high salt dams, lower body weight, higher tail-cuff blood pressure, lower salt sensitivity in females, and increased kidney angiotensin II were observed. Plasma renin activity did not change with changes in salt intake in the adult offspring submitted to high salt environment during the perinatal period. In the offspring, renal mass and the number of glomeruli were not influenced by the dams' salt intake. CONCLUSIONS: Salt overload during pregnancy and/or lactation has long-term effects on offspring's body weight and blood pressure. In addition, high salt diet during the perinatal period induced renin-angiotensin system functional disturbances in the offspring.
Asunto(s)
Presión Sanguínea/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal , Sistema Renina-Angiotensina/fisiología , Cloruro de Sodio Dietético/administración & dosificación , Angiotensina II/análisis , Animales , Animales Recién Nacidos/fisiología , Presión Sanguínea/fisiología , Peso Corporal/efectos de los fármacos , Peso Corporal/fisiología , Femenino , Hipertensión/fisiopatología , Inmunohistoquímica , Riñón/química , Riñón/patología , Embarazo , Ratas , Ratas Wistar , Renina/sangre , Sistema Renina-Angiotensina/efectos de los fármacosRESUMEN
Studies in humans have indicated that dietary salt restriction raises plasma levels of total cholesterol (TC) and triacylglycerols (TAG). In order to explain the mechanisms involved, a rat experimental model was developed consisting of chronic feeding ad libitum isocaloric diets with variable sodium chloride contents. Rates of synthesis of plasma TAG were measured either as the increase of plasma TAG after blocking its removal from plasma by the intra-arterial pulse infusion of Triton-WR 1339, or as the plasma rate of incorporation of [(14)C]-oleic acid [(14)C]-TAG. Plasma TAG removal rate was determined by the intra-arterial pulse infusion of a lipid emulsion. Severe salt restriction increased the plasma concentrations of TAG (71%) and of TC (10%). This result was not due to modification of the rate of synthesis of plasma TAG but was attributed to a 55% slower rate of removal of the TAG-containing lipoproteins. An increased plasma non-esterified fatty acid concentration, probably due to a salt restriction-related insulin resistance, may have impaired the activity of the enzyme lipoprotein lipase.
Asunto(s)
Dieta Hiposódica , Lípidos/sangre , Triglicéridos/sangre , Animales , Masculino , Ácido Oléico/metabolismo , Ratas , Ratas Wistar , Cloruro de Sodio Dietético/farmacologíaRESUMEN
Renal glucose reabsorption is mediated by luminal sodium-glucose cotransporters (SGLTs) and basolateral facilitative glucose transporters (GLUTs). The modulators of these transporters are not known, and their substrates glucose and Na+ are potential candidates. In this study we examined the role of glucose and Na+ filtration rate on gene expression of glucose transporters in renal proximal tubule. SGLT1, SGLT2, GLUT1 and GLUT2 mRNAs were assessed by Northern blotting; and GLUT1 and GLUT2 proteins were assessed by Western blotting. Renal cortex and medulla samples from control rats (C), diabetic rats (D) with glycosuria, and insulin-resistant 15-month old rats (I) without glycosuria; and from normal (NS), low (LS), and high (HS) Na+-diet fed rats were studied. Compared to C and I rats, D rats increased (P < 0.05) gene expression of SGLT2 by approximately 36%, SGLT1 by approximately 20%, and GLUT2 by approximately 100%, and reduced (P < 0.05) gene expression of GLUT1 by more than 50%. Compared to NS rats, HS rats increased (P < 0.05) SGLT2, GLUT2, and GLUT1 expression by approximately 100%, with no change in SGLT1 mRNA expression, and LS rats increased (P < 0.05) GLUT1 gene expression by approximately 150%, with no changes in other transporters. In summary, the results showed that changes in glucose or Na+ filtrated rate modulate the glucose transporters gene expression in epithelial cells of the renal proximal tubule.
Asunto(s)
Regulación de la Expresión Génica , Glucosa/metabolismo , Túbulos Renales Proximales/metabolismo , Proteínas de Transporte de Monosacáridos/genética , Sodio/metabolismo , Animales , Northern Blotting , Western Blotting , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Dieta , Tasa de Filtración Glomerular , Transportador de Glucosa de Tipo 1 , Transportador de Glucosa de Tipo 2 , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Proteínas de Transporte de Monosacáridos/metabolismo , ARN Mensajero , Ratas , Ratas Wistar , Transportador 1 de Sodio-Glucosa , Transportador 2 de Sodio-GlucosaRESUMEN
In the present study we investigated the effect of salt intake on myenteric neuron size of the colon of adult male Wistar rats. The animals were placed on either a high-salt (HS; 8%; 12 animals) or a low-salt diet (LS; 0.15%; 12 animals) for 15 or 52 weeks and blood pressure was measured. The sizes of myenteric neurons of the distal colon from both groups were measured. No difference in neuron size was observed between the HS and LS groups after 15 weeks. After 52 weeks on HS, neuron size was increased (P<0.005) when compared with the LS group. The rats also presented hypertension, which was significantly different at 52 weeks (142 +/- 11 vs 119 +/- 7 mmHg). These results suggest that a long time on an HS diet can significantly increase myenteric nerve cell size.
Asunto(s)
Colon/efectos de los fármacos , Plexo Mientérico/efectos de los fármacos , Neuronas/efectos de los fármacos , Sodio en la Dieta/farmacología , Animales , Colon/inervación , Dihidrolipoamida Deshidrogenasa/metabolismo , Hipertensión/etiología , Hipertrofia/inducido químicamente , Masculino , Plexo Mientérico/enzimología , Neuronas/patología , Ratas , Ratas Wistar , Sodio en la Dieta/administración & dosificaciónRESUMEN
In the present study we investigated the effect of salt intake on myenteric neuron size of the colon of adult male Wistar rats. The animals were placed on either a high-salt (HS; 8 percent; 12 animals) or a low-salt diet (LS; 0.15 percent; 12 animals) for 15 or 52 weeks and blood pressure was measured. The sizes of myenteric neurons of the distal colon from both groups were measured. No difference in neuron size was observed between the HS and LS groups after 15 weeks. After 52 weeks on HS, neuron size was increased (P<0.005) when compared with the LS group. The rats also presented hypertension, which was significantly different at 52 weeks (142 +/- 11 vs 119 +/- 7 mmHg). These results suggest that a long time on an HS diet can significantly increase myenteric nerve cell size.
Asunto(s)
Animales , Ratas , Masculino , Plexo Mientérico/efectos de los fármacos , Neuronas/efectos de los fármacos , Sodio en la Dieta/administración & dosificación , Colon/patología , Dihidrolipoamida Deshidrogenasa/metabolismo , Hipertensión/etiología , Plexo Mientérico/enzimología , Ratas WistarRESUMEN
Because of conflicting results in the literature, further studies are needed to confirm an association between the degree of salt consumption and insulin sensitivity. The aim of this study was to measure insulin sensitivity in rats fed from weaning to adulthood with a low (LSD), normal (NSD), or high (HSD) salt diet. Body weight, carcass lipid content, blood glucose, nonesterified fatty acids, plasma insulin, plasma renin activity, and a glucose transporter (GLUT4) were measured. A euglycemic hyperinsulinemic clamp was used in 52 anesthetized rats. Body weight was higher in rats on LSD than in those on NSD (P<0.05) or HSD (P<0.001). Percentage fat carcass content was higher (P<0.05) in rats on LSD than in those on NSD. Basal plasma insulin and glucose levels were not altered (P>0.05) by salt consumption. Nonesterified fatty acids were lower in rats on HSD than in those on LSD (P<0.05) or NSD (P<0.01). Glucose uptake was lower in rats on LSD than in those on NSD (P<0.05) or HSD (P<0. 001). When a euglycemic hyperinsulinemic clamp was used on pair-weight rats, similar results were obtained, which suggests that the effect of LSD on insulin sensitivity was not due to higher body weight. GLUT4 in insulin-sensitive tissues was increased in rats on HSD except in the cardiac muscle. Captopril treatment partially reversed low insulin sensitivity in LSD rats, whereas losartan did not change it, which indicates that the effect of LSD on insulin sensitivity is angiotensin independent. In conclusion, the present results demonstrate that chronic dietary salt restriction induces a decrease in insulin sensitivity not associated with renin-angiotensin system activity or body weight changes.
Asunto(s)
Envejecimiento/fisiología , Dieta Hiposódica , Resistencia a la Insulina/fisiología , Proteínas Musculares , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Animales , Antihipertensivos/farmacología , Transporte Biológico/efectos de los fármacos , Peso Corporal , Captopril/farmacología , Glucosa/farmacocinética , Transportador de Glucosa de Tipo 4 , Hiperinsulinismo/fisiopatología , Losartán/farmacología , Masculino , Proteínas de Transporte de Monosacáridos/análisis , Ratas , Ratas Wistar , Cloruro de Sodio Dietético/farmacología , DesteteRESUMEN
OBJECTIVE: Some studies have shown that heme oxygenase inhibition increases blood pressure in rats. This effect may be due to the consequent lower levels of the heme degradation products (carbon monoxide, biliverdin, and Fe3+) or due to heme accumulation. However, it is not yet known if the variable effect of NaCl on blood pressure levels is influenced by the heme/heme oxygenase pathway activity. This enzymatic system may be studied by blocking its activity with zinc protoporphyrin IX (ZnPP IX), a heme oxygenase inhibitor. DESIGN AND METHODS: Male Wistar rats were fed from weaning with low (LSD--0.15% NaCl), normal (NSD--1.3% NaCl), or high (HSD--8% NaCl) salt diet On the 12th week of age, assessment of the tail-cuff blood pressure (tc-BP) response to acute inhibition of heme oxygenase with ZnPP IX or after vehicle (Na2CO3) was performed. RESULTS: A higher tc-BP was observed on HSD both before ZnPP IX (P< 0.001) and vehicle (P = 0.003). After ZnPP IX, tc-BP decreased on HSD (P < 0.001) and increased on NSD (P = 0.003) and on LSD (P < 0.001). The area under the curve (AUC) of the percentage change in the blood pressure response was calculated. On putting all the rats from the three dietary groups together, an inverse correlation was observed between individual AUC after ZnPP IX and control tc-BP (r = -0.71; P< 0.001) but not after vehicle (r = 0.34; P < 0.05). CONCLUSIONS: Chronic salt overload increases blood pressure in Wistar rats and the pressure response to heme oxygenase is modulated by the effect of NaCl consumption on blood pressure levels.
Asunto(s)
Presión Sanguínea/fisiología , Hemo Oxigenasa (Desciclizante)/metabolismo , Hemo/metabolismo , Sodio en la Dieta/administración & dosificación , Animales , Presión Sanguínea/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Hemo Oxigenasa (Desciclizante)/antagonistas & inhibidores , Masculino , Protoporfirinas/farmacología , Ratas , Ratas WistarRESUMEN
The effect of sodium chloride salt restriction and overload on insulin sensitivity is still an open question. Some authors have shown that NaCl salt restriction increases insulin resistance, whereas others have reported the opposite. In the present study, the objective was to get some more insight on this issue by studying the influence of dietary salt content on glucose uptake in isolated adipocytes. Male Wistar rats were fed from weaning either low (0.15%) or high (7.94%) salt diets. On the 12th week of age, weight and tail-cuff blood pressure were measured, followed 10 days later by an intravenous glucose tolerance test with concomitant insulin determinations. One week later, the rats were killed by decapitation and epididymal adipocytes were obtained for glucose metabolism evaluation. No weight differences were observed between both groups of animals. Blood pressure was significantly higher (P < .001) on salt overloaded rats (146 +/- 11 mm Hg) than on salt restricted ones (115 +/- 5 mm Hg). Dietary salt content did not influence the area under the curve of plasma glucose. Area under the curve of insulin levels was lower (P = .023) on the high than on the low salt diet. A higher (P < .001) glucose uptake in the absence and in the presence of insulin was observed in adipocytes from rats on the high salt diet. The median effective concentration (EC50) from the dose-response curves of glucose uptake was the same on both groups of animals. Glucose oxidation and incorporation into lipids was also enhanced by salt overload. High salt increased insulin receptor density (P < .001). In conclusion, salt overload increased blood pressure, and high and low salt dietary content did not influence insulin sensitivity based on the unchanged EC50 from the in vitro studies. However, insulin-independent glucose uptake, oxidation, and incorporation into lipids were enhanced in adipocytes from rats on the high salt diet. The lower levels of insulin during the glucose tolerance test on salt-loaded animals may be a consequence of the higher insulin-independent glucose uptake in that group.
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Adipocitos/metabolismo , Presión Sanguínea/efectos de los fármacos , Glucosa/metabolismo , Resistencia a la Insulina/fisiología , Cloruro de Sodio Dietético/farmacología , Adipocitos/efectos de los fármacos , Animales , Antimetabolitos/metabolismo , Peso Corporal/efectos de los fármacos , Creatinina/sangre , Desoxiglucosa/metabolismo , Epidídimo/citología , Epidídimo/metabolismo , Hipertrofia Ventricular Izquierda/inducido químicamente , Técnicas In Vitro , Metabolismo de los Lípidos , Masculino , Oxidación-Reducción , Ratas , Ratas WistarRESUMEN
The objective of this study was to reevaluate salt sensitivity (SENS) after a period of antihypertensive treatment (AT). SENS was measured in ten patients, before and after 18 +/- 6 months on AT. The average for all mean blood pressures (MBP) measured during AT was used as an index of blood pressure (BP) control. After at least eight weeks on placebo only, all patients were submitted to an ad libitum diet (ALD), low salt diet (LSD), and high salt diet (HSD) during one week each. SENS was considered as the percent change of the MBP between the seventh day of LSD and HSD. Weight, BP, and daily urinary Na+ and K+ excretion (mean of seven days) on ALD were the same in the first (F) and second (S) evaluation. SENS did not significantly change from the F and S measurement. An inverse correlation was obtained between individual SENS difference and the average mean blood pressure (AMBP) (r = -0.85, p = 0.0018). In conclusion, patients who showed greater decreases in SENS were the ones with the best BP control.
Asunto(s)
Hipertensión/tratamiento farmacológico , Cloruro de Sodio Dietético/administración & dosificación , Adulto , Presión Sanguínea , Peso Corporal , Femenino , Humanos , Hipertensión/fisiopatología , Masculino , Persona de Mediana EdadRESUMEN
We determined the effect of dietary sodium intake (0.15 and 8% NaCl) on the cardiac neuron size of normotensive 3-week old Wistar rats. An increase in dietary sodium for 48 weeks induced an increase in neuronal size. The number of large neurons (larger than 500 microns 2) increased significantly (chi-square test) in rats ingesting 8% NaCl in their food. The rats presented hypertension (128 +/- 9 vs 134 +/- 16 mmHg; difference not significant, Student t-test) and a statistically significant increase in cardiac muscle mass (1.6 +/- 0.1 vs 2.0 +/- 0.2 mg/g of rat). We conclude that food sodium can significantly increase cardiac nerve cell size and this trophic response occurs concomitantly with an increase of cardiac muscle mass.
Asunto(s)
Cardiomegalia/fisiopatología , Hipertensión/inducido químicamente , Neuronas/efectos de los fármacos , Sodio en la Dieta/farmacología , Animales , Cardiomegalia/etiología , Distribución de Chi-Cuadrado , Hipertensión/etiología , Miocardio/patología , Neuronas/fisiología , Ratas , Ratas WistarRESUMEN
We determined the effect of dietary sodium intake (0.15 and 8 per cent NACl) on the cardiac neuron size of normotensive 3-week old Wistar rats. An increase in dietary sodium for 48 weeks induced an increase in neuronal size. The number of large neurons (larger than 500 muM2) increased significantly (chi-square test) in rats ingesting 8 per cent NaCl in their food. The rats presented hypertension (128 ñ 9 vs 134 ñ 16 mmHg; difference not significant, Student t-test) and a statistically significant increase in cardiac muscle mass (1.6 ñ 0.1 vs 2.0 ñ 0.2 mg/g of rat). We conclude that food sodium can significantly increase cardiac nerve cell size and this trophic response occurs concomitantly with an increase of cardiac muscle mass.
Asunto(s)
Animales , Ratas , Hipertensión/inducido químicamente , Cardiomegalia/fisiopatología , Neuronas , Sodio en la Dieta/farmacología , Hipertensión/etiología , Cardiomegalia/etiología , Miocardio/patología , Neuronas/fisiología , Ratas WistarRESUMEN
In addition to demonstrating evidences of increased sympathetic nervous system activity and marked left ventricular hypertrophy in salt-sensitive hypertensives, our group has also reported increased weight gain with salt overload in these patients. The increased weight gain suggests volume expansion, a situation already shown to increase plasma levels of a Na, K-ATPase inhibitor. Therefore, in the present study, digoxin-like factor (DLF) serum levels, spontaneous salt ingestion, nifedipine hypotensive effect, and plasma renin activity were evaluated in essential hypertensive subjects. Thirteen essential hypertensive outpatients were studied sequentially on an ad lib diet, a low salt diet (LSD = 30 mEq Na/day), and a high salt diet (HSD = LSD + 171 mmol/L NaCl/day), 1 week each. On the seventh day of LSD and HSD, DLF levels, mean blood pressure (MBP) response to nifedipine (10 mg sublingual), and plasma renin activity were measured. The MBP percent change from the seventh day of LSD to the seventh day of HSD (salt sensitivity) ranged from -13.7 to 20.9%. A positive correlation (r = 0.64, P < .01) was observed between salt sensitivity and 24-h urinary sodium excretion with an ad lib diet. The DLF serum levels correlated with the salt sensitivity both on LSD (r = 0.50, P < .05) and on HSD (r = 0.53, P < .05). Salt sensitivity was positively correlated with the difference of response to nifedipine between HSD and LSD (r = 0.78, P < .001). Plasma renin activity correlated inversely with DLF on LSD (r = -0.51, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Proteínas Sanguíneas/análisis , Dieta Hiposódica , Digoxina , Hipertensión/fisiopatología , Nifedipino/uso terapéutico , Saponinas , Cloruro de Sodio/farmacología , Adulto , Presión Sanguínea/efectos de los fármacos , Cardenólidos , Femenino , Humanos , Hipertensión/sangre , Hipertensión/tratamiento farmacológico , Masculino , Persona de Mediana EdadRESUMEN
Besides the duration and severity of hypertension, several other factors have been shown to be related to left ventricular hypertrophy (LVH) in essential hypertension. The present study was conducted to examine the influence of salt sensitivity on LVH. Fifteen essential hypertensive ambulatory patients were submitted to a low-salt (30 mEq of Na/day for 7 days) and a high-salt (200 mEq of Na/day for 7 days) diet after 12 weeks on placebo. Daily urine collection was obtained during the whole study. After the placebo period, all patients were submitted to a complete clinical and laboratory investigation that included an echocardiogram (M-mode and two-dimensional). Five patients were salt-sensitive (mean blood pressure (BP) increase from the seventh day of the low- to the seventh day of the high-salt diet greater than 10%). No differences in weight, sex ratio, and duration of hypertension were obtained between salt-sensitive and -resistant patients. The initial BP was higher in the salt-sensitive patients. However, the difference was small and without statistical significance. The left ventricular weight was higher in the salt-sensitive than in salt-resistant patients (148 +/- 51 vs. 109 +/- 32 g/m2, p less than 0.05). The left ventricular end-diastolic diameter was also higher in the salt-sensitive patients (50 +/- 10 vs. 43 +/- 6 mm, p less than 0.05). The interventricular septum and posterior wall thicknesses were higher in salt-sensitive patients, although they did not reach statistical significance. In conclusion, salt-sensitive essential hypertensive patients are at a higher risk to develop LVH.
Asunto(s)
Cardiomegalia/inducido químicamente , Hipertensión/complicaciones , Sodio en la Dieta/efectos adversos , Adulto , Presión Sanguínea/efectos de los fármacos , Cardiomegalia/etiología , Ecocardiografía , Humanos , Persona de Mediana Edad , Sodio en la Dieta/orinaRESUMEN
We studied the acute effect of oral captopril (25mg) and clonidine(300 micrograms) on blood pressure (BP) in patients with essential hypertension successively maintained on a low (LSD) and high (HSD) salt diet. Seven patients were salt sensitive (SS) and seven were salt resistant (SR). The maximal decrease in diastolic BP caused by captopril in patients on the LSD was greater in SS than SR individuals. Baseline urinary norepinephrine levels did not change from LSD to HSD (p greater than 0.05) in SS patients and decreased in SR patients (p less than 0.05). The maximal decrease in mean BP during the clonidine test was the same for both diets (p greater than 0.05) in SS patients and was lower (p less than 0.05) for the HSD in SR patients. SS patients on the HSD presented a higher decrease in systolic BP than SR patients (p less than 0.05) during the clonidine test. These data suggest overactivity of the renin-angiotensin system in SS patients on the LSD and of the sympathetic nervous system in SS patients on the HSD and that the clonidine test could be a good indicator for identifying SS and SR patients.