RESUMO
Under high sodium intake renal dopamine (DA) increases while NOS I expression in macula densa cells (MD) decreases. To explore whether renal DA and NOS I, linked to natriuresis and to the stability of the tubuloglomerular feedback, respectively, act in concert to regulate renal plasma flow (RPF) and glomerular filtration rate (GFR). Male Wistar rats were studied under a normal sodium intake (NS, NaCl 0.24%) or a high sodium intake (HS, NaCl 1% in drinking water) during the 5 days of the study. For the last two days, the specific D1-like receptor antagonist SCH 23390 (1 mg kg bwt-1 day-1, sc) or a vehicle was administered. HS intake increased natriuresis, diuresis, and urinary DA while it decreased cortical NOS I expression (P < 0.05 vs. NS), Nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) activity in MD (P < 0.001 vs. NS) and cortical nitrates+nitrites (NOx) production (NS 2.04 ± 0.22 vs. HS 1.28 ± 0.10 nmol mg protein-1, P < 0.01). Treatment with SCH 23390 to rats on HS sharply decreased hydroelectrolyte excretion (P < 0.001 vs. HS) while NOS I expression, NADPH-d activity and NOx production increased (P < 0.05 vs. HS for NOS I and P < 0.001 vs. HS for NADPH-d and NOx). SCH 23390 increased RPF and GFR in HS rats (P < 0.01 HS+SCH vs. HS). It did not cause variations in NS rats. Results indicate that when NS intake is shifted to a prolonged high sodium intake, renal DA through the D1R, and NOS I in MD cells act in concert to regulate RPF and GFR to stabilize the delivery of NaCl to the distal nephron.
Assuntos
Taxa de Filtração Glomerular/fisiologia , Córtex Renal/metabolismo , Fluxo Plasmático Renal/fisiologia , Cloreto de Sódio/metabolismo , Sódio na Dieta , Animais , Benzazepinas/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Dopamina/metabolismo , Antagonistas de Dopamina/farmacologia , Taxa de Filtração Glomerular/efeitos dos fármacos , Córtex Renal/efeitos dos fármacos , Masculino , NADP/metabolismo , Natriurese/efeitos dos fármacos , Natriurese/fisiologia , Óxido Nítrico Sintase Tipo I/metabolismo , Ratos , Ratos Wistar , Fluxo Plasmático Renal/efeitos dos fármacosRESUMO
Pregnancy is characterized by maternal systemic and intrarenal vasodilation, leading to increases in the renal plasma flow (RPF) and glomerular filtration rate (GFR). These responses are mainly mediated by nitric oxide (NO) and relaxin. The impact of cigarette smoking on the maternal adaptations to pregnancy is unclear. Here we evaluated the effects of chronic exposure to nicotine on systemic and intrarenal parameters in virgin (V) and 14-day pregnant (P) Wistar rats. V and P groups received saline or nicotine (6 mg·kg(-1)·day(-1)) respectively, via osmotic minipumps for 28 days, starting 14 days before pregnancy induction. Nicotine induced a 10% increase in blood pressure in the V group and minimized the characteristic pregnancy-induced hypotension. Renal sympathetic nerve activity (rSNA) and baroreflex sensitivity were impaired by nicotine mainly in the P group, indicating that the effect of nicotine on blood pressure was not mediated by nervous system stimulation. Nicotine had no effect on GFR in the V rats but reduced GFR of the P group by 30%. Renal expression of sodium and water transporters was downregulated by nicotine, resulting in increased fractional sodium excretion mainly in the P group, suggesting that nicotine compromised the sodium and water retention required for normal gestation. There was a reduction in the expression of inducible NO synthase (iNOS) in both the kidney tissue and renal artery, as well as in the expression of the relaxin receptor (LGR7). These results clearly show that nicotine induced deleterious effects in both virgin and pregnant animals, and abolished the maternal capacity to adapt to pregnancy.
Assuntos
Adaptação Fisiológica/efeitos dos fármacos , Exposição Ambiental/efeitos adversos , Taxa de Filtração Glomerular/efeitos dos fármacos , Nicotina/efeitos adversos , Fluxo Plasmático Renal/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Animais , Barorreflexo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Feminino , Rim/fisiopatologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/biossíntese , Gravidez , Ratos , Ratos Wistar , Receptores Acoplados a Proteínas G/biossíntese , Receptores de Peptídeos/biossíntese , Relaxina/metabolismo , Sistema Nervoso Simpático/fisiologia , Vasodilatação/fisiologiaRESUMO
We evaluated whether the blockade of the proinflammatory transcription factor NF-kappaB would modify the oxidative stress, inflammation, and structural and hemodynamic alterations found in the kidney as a result of massive proteinuria. Twenty male Sprague-Dawley rats were injected with 2 g of BSA intraperitoneally daily for 2 wk. Ten of them received in addition the inhibitor of NF-kappaB activation pyrrolidine dithiocarbamate (PDTC; 200 mg.kg(-1).day(-1) sc) and the rest received vehicle. Seven rats that received intraperitoneal saline were used as controls. Glomerular hemodynamics were studied after 14 days. Markers of oxidative stress (NF-kappaB subunit p65+ cells, 3-nitrotyrosine, and 4-hydroxynonenal), inflammation (cortical CD68+ cells and NOS-II), and afferent arteriole damage were assessed by immunohistochemistry and morphometry. Activity of antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase was evaluated in renal cortex and medulla. Albumin overload induced massive proteinuria, oxidative stress with reduced activity of antioxidant enzymes, NF-kappaB activation, inflammatory cell infiltration, a significant presence of proteinaceous casts, systemic and glomerular hypertension, as well as arteriolar remodeling. Treatment with PDTC prevented or improved all of these findings. In this model of nephrotic syndrome, we demonstrate a key role for oxidative stress and inflammation in causing systemic and glomerular hypertension and proteinuria. Oxidative stress and inflammation may have a key role in accelerating renal injury associated with intense proteinuria.
Assuntos
Hipertensão Renal/tratamento farmacológico , Glomérulos Renais/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Proteinúria/tratamento farmacológico , Pirrolidinas/farmacologia , Tiocarbamatos/farmacologia , Aldeídos/metabolismo , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Taxa de Filtração Glomerular/efeitos dos fármacos , Taxa de Filtração Glomerular/fisiologia , Glutationa Redutase/metabolismo , Hipertensão Renal/fisiopatologia , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/fisiopatologia , Glomérulos Renais/fisiopatologia , Masculino , Óxido Nítrico Sintase Tipo II/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Peroxidases/metabolismo , Proteinúria/fisiopatologia , Pirrolidinas/uso terapêutico , Ratos , Ratos Sprague-Dawley , Fluxo Plasmático Renal/efeitos dos fármacos , Fluxo Plasmático Renal/fisiologia , Superóxido Dismutase/metabolismo , Tiocarbamatos/uso terapêutico , Fator de Transcrição RelA/metabolismo , Tirosina/análogos & derivados , Tirosina/metabolismoRESUMO
OBJECTIVE: The aim of the study was to determine the possible role of NO-system activation in vascular and renal effects of the dopaminergic system and the probable interaction between both systems during acute volume expansion in rats. DESIGN AND METHODS: Expanded (10% bw) and non-expanded anaesthetized male Wistar rats were treated with haloperidol, a DA receptor antagonist (3 mg/kg bw, ip). Mean arterial pressure, diuresis, natriuresis, renal plasma flow, glomerular filtration rate, nitrites and nitrates excretion (NOx) were determined. NADPH diaphorase activity was measured using a histochemistry technique in kidney, aorta and renal arteries. NOS activity in kidney and aorta from expanded and non-expanded animals was determined with L-[U14C]-arginine substrate, in basal conditions and after DA (1 microM) administration. RESULTS: The hypotensive effect of L-arg and hypertension induced by L-NAME were not modified by haloperidol. This blocker reverted the increase in diuresis, natriuresis and RPF induced by L-arg in both groups. Dopaminergic blockade induced a decrease in NOx excretion and in NADPH-diaphorase activity in glomeruli, proximal tubule and medullar collecting duct and in endothelium and vascular smooth muscle of renal arteries. DA induced an increase in NOS activity in renal medulla and cortex in both groups, but no changes in the aorta were observed. CONCLUSIONS: Our results suggest that renal DA would be associated with the renal response induced by NO during extracellular volume expansion. NO-system activation would be one of the mechanisms involved in renal DA activity during saline load, but NO appears not to be involved in DA vascular effects.
Assuntos
Dopamina/metabolismo , Rim/metabolismo , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico/fisiologia , Fluxo Plasmático Renal , Animais , Aorta/efeitos dos fármacos , Aorta/enzimologia , Arginina/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Citrulina/análise , Diurese/efeitos dos fármacos , Antagonistas de Dopamina/farmacologia , Líquido Extracelular/efeitos dos fármacos , Haloperidol/farmacologia , Rim/irrigação sanguínea , Rim/efeitos dos fármacos , Masculino , NADPH Desidrogenase/análise , NADPH Desidrogenase/metabolismo , NG-Nitroarginina Metil Éster/farmacologia , Natriurese/efeitos dos fármacos , Nitratos/metabolismo , Óxido Nítrico Sintase/antagonistas & inibidores , Nitritos/metabolismo , Ratos , Ratos Wistar , Artéria Renal/efeitos dos fármacos , Artéria Renal/enzimologia , Fluxo Plasmático Renal/efeitos dos fármacosRESUMO
BACKGROUND: The aim of the present study was to evaluate the long-term effects of oral creatine supplementation on renal function and body composition (fat and lean mass) in an experimental model. METHODS: Male Wistar rats were supplemented with creatine (2 g.kg(-1) of food) for 10 wk in combination with treadmill exercise, 12 m.min(-1), 1 h.d(-1) (CREAT + EX, N = 12) or not (CREAT, N = 10), and compared with exercised animals without creatine supplementation (EX, N = 7) and CONTROL animals, N = 7. Body composition and bone mineral density (BMD) were determined by dual x-ray absorptiometry and glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by inulin and paraaminohippurate clearance, respectively. RESULTS: At the end of the study (post), CREAT+EX presented higher lean mass and lower fat mass than CREAT, EX or CONTROL (349.7 +/- 19.7 vs 313.3 +/- 20.3, 311.9 +/- 30.8, 312.4 +/- 21.0 g and 5.7 +/- 2.3 vs 10.0 +/- 3.3, 9.8 +/- 1.5, 10.0 +/- 3.5%, P < 0.05, respectively). Post lean/fat mass ratio was higher than baseline only in CREAT + EX (18.9 +/- 7.2 vs 8.6 +/- 1.8, P < 0.05). Post BMD was significantly higher than baseline in all groups. GFR and RPF were lower in CREAT versus CONTROL (0.5 +/- 0.1 vs 1.0 +/- 0.1 and 1.5 +/- 0.2 vs 2.4 +/- 0.5 mL.min(-1), P < 0.05, respectively). CONCLUSION: Creatine supplement in combination with exercise increased the proportion of lean mass more than EX or CREAT alone. The use of creatine alone induced an important and significant reduction of both RPF and GFR.
Assuntos
Composição Corporal/efeitos dos fármacos , Creatina/farmacologia , Suplementos Nutricionais , Dopagem Esportivo/métodos , Rim/efeitos dos fármacos , Condicionamento Físico Animal , Animais , Peso Corporal/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Taxa de Filtração Glomerular/efeitos dos fármacos , Rim/patologia , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Tamanho do Órgão , Ratos , Ratos Wistar , Valores de Referência , Fluxo Plasmático Renal/efeitos dos fármacosRESUMO
Normal aging is accompanied by renal functional and morphological deterioration and dietetic manipulation has been used to delay this age-related decline. We examined the effects of chronic administration of diets containing 5 percent lipid-enriched diet (LD, w/w) on renal function of rats at different ages. Three types of LD were tested: canola oil, fish oil and butter. Mean systemic tail-cuff blood pressure and glycemia remained within the normal range whatever the age and the diet of the animals. Proteinuria began to rise from the 8th month in the groups ingesting LD, while in the control group it increased significantly (above 10 mg/24 h) only after the 10th month. With age, a significant and progressive decline in glomerular filtration rate (GFR) and renal plasma flow was observed in the LD groups but after 6 months of lipid supplementation, the decline in these parameters was more marked in the butter and fish oil groups. By the 18th month, the lowest GFR level was observed in the group ingesting the butter diet (2.93 + or - 0.22 vs 5.01 + or - 0.21 ml min-1 kg-1 in control, P<0.05). Net acid excretion, evaluated in 9- and 18-month-old rats, was stimulated in the fish oil group when compared both to control and to the other two LD groups. These results suggest that even low levels of LD in a chronic nutritional regimen can modify the age-related changes in renal function and that the impact of different types of lipid-supplemented diets on renal function depends on the kind of lipid present in the diet
Assuntos
Animais , Ratos , Rim/fisiologia , Lipídeos/administração & dosagem , Fatores Etários , Análise de Variância , Gorduras na Dieta/administração & dosagem , Taxa de Filtração Glomerular/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/metabolismo , Ratos Wistar , Fluxo Plasmático Renal/efeitos dos fármacosRESUMO
During the development of cirrhosis ascites-edema, peripheral vasodilatation, hypotension and an increase of the plasma concentration of several neurohormones are frequently observed. Such complex changes in the hormonal profile hinders the assessment of the relative role of each in the pathophysiology of this disease. The purpose of this work was to evaluate in a rat model of experimental cirrhosis (phenobarbital/CCl4) the role of the renin-angiotensin system in the pre-ascitic stage of the disease using the converting enzyme inhibitor captopril. Cirrhotic rats showed diminished renal and hepatic perfusion. Compared to normal rats, glomerular filtration rate in cirrhotic rats was reduced from 0.75 +/- 0.11 to 0.42 +/- 0.06 mL/min/100 g BW, and renal plasma flow was reduced from 2.37 +/- 0.28 to 1.58 +/- 0.16 mL/min/100 g BW; the indocyanine green slope changed from -0.095 +/- 0.028 to -0.057 +/- 0.01; the plasma sodium concentration fell from 144 +/- 1.5 to 131 +/- 5.40 mEq/L (all < .05). The mean arterial pressure was not reduced in the cirrhotic rats. There was no ascites. Both the acute (25 mg i.v.) and chronic (25 mg i.p. daily plus 25 mg/L in drinking water) administration of captopril to cirrhotic rats induced an increase in glomerular filtration rate and renal plasma flow along with a steeper slope in indocyanine green decay (p < .05 for all three parameters) when compared to non-treated cirrhotic animals. No changes were observed in controls. In the balance studies, an increase in urinary volume along with a decrease in urinary osmolality was recorded in cirrhotic rats on chronic captopril treatment. In conclusion, our results show an activation of the renin-angiotensin system in these rats, as disclosed by the inhibition of the converting enzyme, as well as a possible interaction with ADH.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Captopril/farmacologia , Cirrose Hepática Experimental/fisiopatologia , Sistema Renina-Angiotensina/fisiologia , Animais , Taxa de Filtração Glomerular/efeitos dos fármacos , Testes de Função Hepática , Masculino , Ratos , Ratos Wistar , Fluxo Plasmático Renal/efeitos dos fármacos , Sistema Renina-Angiotensina/efeitos dos fármacos , Equilíbrio Hidroeletrolítico/efeitos dos fármacosRESUMO
The role of catecholamines in the distribution of intrarenal blood flow and in single-nephron glomerular filtration rate (SNGFR) was evaluated in anesthetized Wistar rats by the Hanssen technique. Epinephrine (EPI) and norepinephrine (NOR) were infused to produce elevations of 20-30 mmHg in mean arterial pressure. Superficial and juxtamedullary nephron perfusion and filtration were determined by the presence of Prussian blue dye. In the control group, 100% of the nephrons presented a homogeneous pattern of perfusion and filtration. In contrast, a heterogeneous distribution of the dye was found even in the larger arteries (arciform and radial), indicating variable perfusion and filtration in both superficial and juxtamedullary nephrons. The effects of EPI and NOR were also evaluated in the superficial cortex by the micropuncture technique in two additional groups of Munich-Wistar rats. Mean SNGFR was 27% and 54% lower in the EPI- and NOR-treated groups, respectively. No change in mean intraglomerular hydraulic pressure was observed after EPI or NOR infusion in spite of a highly scattered pattern, indicating an important variability in perfusion along the superficial cortex, and/or different sensitivity of the pre- and post-glomerular arterioles. The present data suggest that EPI and NOR may affect intrarenal hemodynamics by modifying perfusion and filtration in both superficial and juxtamedullary glomeruli and not by shifting blood flow from superficial to juxtamedullary nephrons. The heterogeneous pattern of perfusion was a consequence of differential vasoconstriction along the intrarenal arteries, probably due to different density and/or sensitivity of the adrenergic receptor subtypes present in the intrarenal vascular tree.
Assuntos
Epinefrina/farmacologia , Taxa de Filtração Glomerular/efeitos dos fármacos , Norepinefrina/farmacologia , Animais , Catecolaminas/farmacologia , Masculino , Ratos , Ratos Wistar , Fluxo Plasmático Renal/efeitos dos fármacosRESUMO
The role of catecholamines in the distribution of intrarenal blood flow and in single-nephron glomerular filtration rate (SNGFR) was evaluated in anesthetized Wistar rats by the Hanssen technique. Epinephrine (EPI) and norepinephrine (NOR) were infused to produce elevations of 20-30 mmHg in mean arterial pressure. Superficial and juxtamedullary nephron perfusion and filtration were determined by the presence of Prussian blue dye. In the control group, 100 per cent of the nephrons presented a homogeneous pattern of perfusion and filtration. In contrast, a heterogenous distribution of the dye was found even in the larger arteries (arciform and radial), indicating variable perfusion and filtration in both superficial and juxtamedullary nephrons. The effects of EPI and NOR were also evaluated in the superficial cortex by the micropuncture technique in two additional groups of Munich-Wistar rats. Mean SNGFR was 27 per cent and 54 per cent lower in the EPI-and NOR-treated groups, respectively. No change in mean intraglomerular hydraulic pressure was observed after EPI or NOR infusion in spite of a highly scattered pattern, indicating an important variability in perfusion along the superficial cortex, and/or different sensitivity of the pre-and post-glomerular arterioles. The present data suggest that EPI and NOR may affect intrarenal hemodynamics by modifying perfusion and filtration in both superficial and juxtamedullary glomeruli and not by shifting blood folow from superficial to juxtamedullary nephrons. The heterogenous pattern of perfusion was a consequence of differential vasoconstriction along the intrarenal arteries, probably due to different density and/or sensitivity of the adrenergic receptor subtypes present in the intrarenal vascular tree.
Assuntos
Ratos , Animais , Epinefrina/farmacologia , Taxa de Filtração Glomerular/efeitos dos fármacos , Norepinefrina/farmacologia , Catecolaminas/farmacologia , Ratos Wistar , Fluxo Plasmático Renal/efeitos dos fármacosRESUMO
1. The effects of verapamil (V, 0.015 mg/min, i.v.) or CaCl2 (800 mEq/l, 0.025 ml kg-1 min-1, i.v.) on renal function and mean arterial pressure (MAP) were evaluated in male Wistar rats weighing 280-320 g during treatment with stevioside (S, 16 mg kg-1 h-1, i.v.). 2. Verapamil administered to 10 rats significantly increased the hypotensive effect of stevioside on MAP (control, 124 +/- 0.77; S, 96 +/- 1.50; S+V, 67 +/- 0.70 mmHg) and on fractional sodium excretion (control, 0.76 +/- 0.05; S, 1.56 +/- 0.10; S+V, 2.72 +/- 0.25%). Urinary flow, reported as percent glomerular filtration rate (V/GFR), and renal plasma flow (RPF) increased slightly but not significantly during stevioside plus verapamil administration. 3. In contrast, infusion of CaCl2 in 10 rats pretreated with stevioside induced a marked attenuation of MAP (control, 119 +/- 1.83; S, 70 +/- 1.12; S+CaCl2, 109 +/- 1.60 mmHg) and RPF (control, 16.73 +/- 3.76; S, 34.33 +/- 2.55; S+CaCl2, 17.20 +/- 2.87 ml min-1 kg-1). The diuresis and natriuresis induced by stevioside were also inhibited by simultaneous administration of CaCl2. 4. These data are consistent with the view that stevioside acts on arterial pressure and renal function as a calcium antagonist, as is the case for verapamil.