RESUMO
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.
Assuntos
Cardiomegalia/prevenção & controle , Fármacos Cardiovasculares/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Receptor Tipo 2 de Angiotensina/agonistas , Cloreto de Sódio na Dieta , Sulfonamidas/farmacologia , Tiofenos/farmacologia , Remodelação Ventricular/efeitos dos fármacos , Animais , Pressão Sanguínea/efeitos dos fármacos , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Cardiomegalia/fisiopatologia , Modelos Animais de Doenças , Fibrose , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Hipertensão/prevenção & controle , Masculino , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Ratos Wistar , Receptor Tipo 2 de Angiotensina/metabolismo , Transdução de Sinais , Aumento de Peso/efeitos dos fármacosRESUMO
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.
RESUMO
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.
Assuntos
Miocárdio/ultraestrutura , Cloreto de Sódio na Dieta/administração & dosagem , Cloreto de Sódio na Dieta/efeitos adversos , Angiotensina II/sangue , Animais , Pressão Sanguínea/efeitos dos fármacos , Ecocardiografia , Feminino , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/fisiopatologia , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , Potássio/sangue , Gravidez , Efeitos Tardios da Exposição Pré-Natal/etiologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Ratos , Ratos Wistar , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Renina-Angiotensina/genética , Sódio/sangue , Sódio/urinaRESUMO
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.
Assuntos
Angiotensinogênio/genética , Angiotensinas/genética , Cloreto de Sódio na Dieta/farmacologia , Sistema Nervoso Simpático/efeitos dos fármacos , Angiotensina I/sangue , Angiotensina I/genética , Angiotensina I/metabolismo , Angiotensina II/sangue , Angiotensina II/genética , Angiotensina II/metabolismo , Angiotensinogênio/sangue , Angiotensinogênio/metabolismo , Angiotensinas/sangue , Angiotensinas/metabolismo , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Hipertensão/induzido quimicamente , Hipertensão/fisiopatologia , Rim/efeitos dos fármacos , Rim/inervação , Rim/metabolismo , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Renina/sangue , Renina/genética , Renina/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sistema Nervoso Simpático/fisiologiaRESUMO
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.