RESUMO
The offspring of coronary heart disease (CHD) patients are at particularly high risk for developing CHD. Endothelial dysfunction is present in the majority of CHD and atherosclerosis patients. Fish oil, rich in n-3 fatty acids has been shown to augment endothelium-dependent vasodilatation in human peripheral and coronary arteries. The aims of this study are to investigate presence of endothelial dysfunction determined by the brachial flow-mediated diameter, nitric oxide, plasma lipids and fibrinogen, and the effect of high doses of fish oil on these parameters. Twenty-four healthy offspring of CHD patients (study group) were supplemented with 9 g/day Alsepa fish oil (each gram containing 180 mg EPA and 120 mg DHA), for a period of two weeks. Plasma nitric oxide, urine nitric oxide, fibrinogens and flow-mediated vasodilatation (FMD) were determined prior to fish oil therapy, two weeks into therapy and four weeks after the end of therapy with fish oil. Twelve healthy subjects (control group) with no family history of heart disease were studied as controls (day one only). The offspring had a lower increase in FMD and lower nitric oxide production, compared with the control group. No other parameters varied between the two groups. The administration of fish oil did not result in any changes in the studied parameters. In healthy offspring of CHD patients, early endothelial dysfunction was documented before evidence of atherosclerosis. Ingestion of fish oil over a 13-day period did not improve endothelial dysfunction.
Assuntos
Endotélio Vascular/fisiopatologia , Óleos de Peixe/farmacologia , Isquemia Miocárdica/genética , Óxido Nítrico/biossíntese , Adulto , Artéria Braquial/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/prevenção & controle , Vasodilatação/efeitos dos fármacosRESUMO
Anemia (Hemoglobin of < 12 to 13 g/dl) is frequently encountered in patients with congestive heart failure (CHF). This anemia may be partly due to hemodilution, partly to the associated reduction in renal function, and partly to the use of ACE inhibitors and aspirin. However, there is evidence that CHF alone--through excessive cytokine production may also reduce the bone marrow and cause anemia. In several recent studies anemia has been found to be associated with a more severe degree of CHF, a higher rate of death, renal failure, hospitalization and evidence of malnutrition. In both uncontrolled and controlled studies correction of anemia with erythropoietin with or without the addition of i.v. iron has been attempted. The correction of anemia has been associated with a marked improvement in New York Heart Association (NYHA) functional cardiac class and Left Ventricular Ejection Fraction, a marked reduction in the need for hospitalization and high dose oral and i.v. diuretics, and an improvement in exercise capacity, peak exercise oxygen utilization and quality of life. The serum creatinine, which had been increasing steadily before treatment, stabilized with the correction of anemia. All this suggests that control of anemia in CHF could become a valuable addition to the therapeutic armamentarium of CHF and might also play a major role in the prevention of progressive renal failure.
Assuntos
Anemia/complicações , Anemia/terapia , Insuficiência Cardíaca/complicações , Hospitalização , Nefropatias/complicações , Falência Renal Crônica/prevenção & controle , Anemia/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Humanos , Nefropatias/fisiopatologia , Nefropatias/terapia , Falência Renal Crônica/fisiopatologia , SíndromeRESUMO
BACKGROUND: Excess cardiovascular mortality has been documented in chronic haemodialysis patients. Oxidative stress is greater in haemodialysis patients with prevalent cardiovascular disease than in those without, suggesting a role for oxidative stress in excess cardiovascular disease in haemodialysis. We investigated the effect of high-dose vitamin E supplementation on cardiovascular disease outcomes in haemodialysis patients with pre-existing cardiovascular disease. METHODS: Haemodialysis patients with pre-existing cardiovascular disease (n=196) aged 40-75 years at baseline from six dialysis centres were enrolled and randomised to receive 800 IU/day vitamin E or matching placebo. Patients were followed for a median 519 days. The primary endpoint was a composite variable consisting of: myocardial infarction (fatal and non-fatal), ischaemic stroke, peripheral vascular disease (excluding the arteriovenous fistula), and unstable angina. Secondary outcomes included each of the component outcomes, total mortality, and cardiovascular-disease mortality. FINDINGS: A total of 15 (16%) of the 97 patients assigned to vitamin E and 33 (33%) of the 99 patients assigned to placebo had a primary endpoint (relative risk 0.46 [95% CI 0.27-0.78], p=0.014). Five (5.1%) patients assigned to vitamin E and 17 (17.2%) patients assigned to placebo had myocardial infarction (0.3 [0.11-0.78], p=0.016). No significant differences in other secondary endpoints, cardiovascular disease, or total mortality were detected. INTERPRETATION: In haemodialysis patients with prevalent cardiovascular disease, supplementation with 800 IU/day vitamin E reduces composite cardiovascular disease endpoints and myocardial infarction.
Assuntos
Antioxidantes/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Falência Renal Crônica/terapia , Vitamina E/uso terapêutico , Idoso , Antioxidantes/efeitos adversos , Doenças Cardiovasculares/complicações , Deglutição/efeitos dos fármacos , Método Duplo-Cego , Feminino , Seguimentos , Gastroenteropatias/induzido quimicamente , Humanos , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Prurido/induzido quimicamente , Diálise Renal , Análise de Sobrevida , Resultado do Tratamento , Vitamina E/efeitos adversosRESUMO
OBJECTIVES: This study evaluated the prevalence and severity of anemia in patients with congestive heart failure (CHF) and the effect of its correction on cardiac and renal function and hospitalization. BACKGROUND: The prevalence and significance of mild anemia in patients with CHF is uncertain, and the role of erythropoietin with intravenous iron supplementation in treating this anemia is unknown. METHODS: In a retrospective study, the records of the 142 patients in our CHF clinic were reviewed to find the prevalence and severity of anemia (hemoglobin [Hb] <12 g). In an intervention study, 26 of these patients, despite maximally tolerated therapy of CHF for at least six months, still had had severe CHF and were also anemic. They were treated with subcutaneous erythropoietin and intravenous iron sufficient to increase the Hb to 12 g%. The doses of the CHF medications, except for diuretics, were not changed during the intervention period. RESULTS: The prevalence of anemia in the 142 patients increased with the severity of CHF, reaching 79.1% in those with New York Heart Association class IV. In the intervention study, the anemia of the 26 patients was treated for a mean of 7.2 +/- 5.5 months. The mean Hb level and mean left ventricular ejection fraction increased significantly. The mean number of hospitalizations fell by 91.9% compared with a similar period before the study. The New York Heart Association class fell significantly, as did the doses of oral and intravenous furosemide. The rate of fall of the glomerular filtration rate slowed with the treatment. CONCLUSIONS: Anemia is very common in CHF and its successful treatment is associated with a significant improvement in cardiac function, functional class, renal function and in a marked fall in the need for diuretics and hospitalization.
Assuntos
Anemia Ferropriva/tratamento farmacológico , Eritropoetina/administração & dosagem , Insuficiência Cardíaca/complicações , Ferro/administração & dosagem , Idoso , Anemia Ferropriva/epidemiologia , Anemia Ferropriva/etiologia , Anemia Ferropriva/fisiopatologia , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Taxa de Filtração Glomerular/fisiologia , Insuficiência Cardíaca/fisiopatologia , Hospitalização/estatística & dados numéricos , Humanos , Injeções Intravenosas , Injeções Subcutâneas , Masculino , Prevalência , Estudos Retrospectivos , Índice de Gravidade de Doença , Volume Sistólico/efeitos dos fármacos , Volume Sistólico/fisiologiaRESUMO
OBJECTIVES: To determine, in a prospective randomized, double-blind placebo-controlled study, the effect of 6 weeks of high-dose (5 g/day) orally administered nitric oxide (NO) donor L-arginine on men with organic erectile dysfunction (ED). PATIENTS AND METHODS: The study included 50 men with confirmed organic ED who were randomized after a 2-week placebo run-in period to receive L-arginine or placebo. A detailed medical and sexual history, O'Leary's questionnaire, a specially designed sexual function questionnaire and a sexual activity diary were obtained for each patient. All participants underwent a complete physical examination including an assessment of bulbocavernosus reflex and penile haemodynamics. Plasma and urine nitrite and nitrate (designated NOx), both stable metabolites of nitric oxide, were determined at the end of the placebo run-in period, and after 3 and 6 weeks. RESULTS: Nine of 29 (31%) patients taking L-arginine and two of 17 controls reported a significant subjective improvement in sexual function. All objective variables assessed remained unchanged. All nine patients treated with L-arginine and who had subjectively improved sexual performance had had an initially low urinary NOx, and this level had doubled at the end of the study. CONCLUSIONS: Oral administration of L-arginine in high doses seems to cause significant subjective improvement in sexual function in men with organic ED only if they have decreased NOx excretion or production. The haemodynamics of the corpus cavernosum were not affected by oral L-arginine at the dosage used.
Assuntos
Arginina/administração & dosagem , Impotência Vasculogênica/tratamento farmacológico , Doadores de Óxido Nítrico/administração & dosagem , Administração Oral , Idoso , Método Duplo-Cego , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Prospectivos , Comportamento Sexual , Resultado do TratamentoRESUMO
This article, based on our own studies and those of others, presents evidence to show that the anemia of chronic renal failure in the predialysis period is, to a significant extent, caused by iron deficiency and can be improved in most cases by the administration of intravenous (i.v.) but not oral iron. We estimate that in approximately 30% of all predialysis patients with anemia, a target hematocrit (Hct) of 35% can be reached and maintained by giving i.v. iron alone without exceeding currently acceptable limits of serum ferritin (500 microg/liter) or the percentage of iron saturation (40%). If, in addition, subcutaneous erythropoietin (EPO-usually in only low doses-is added, the combination has an additive effect on the Hct response, and almost all anemic predialysis patients can reach and maintain the target Hct of 35% over a one-year period. Therefore, the advantage of maintaining adequate iron stores with i.v. iron is that if EPO is needed, lower doses will be required to achieve the target Hct than if EPO were used alone. This not only avoids the high cost of EPO therapy but also its associated side-effects, especially hypertension. Using Venofer, a ferric hydroxide sucrose complex, as our i.v. iron supplement, we have seen no anaphylactic reactions in over 20,000 infusions over a four-year period in 360 hemodialysis, 123 predialysis, and 58 peritoneal dialysis patients.
Assuntos
Anemia Ferropriva/tratamento farmacológico , Anemia Ferropriva/etiologia , Deficiências de Ferro , Ferro/administração & dosagem , Falência Renal Crônica/complicações , Administração Oral , Anemia Ferropriva/sangue , Pressão Sanguínea/efeitos dos fármacos , Doença das Coronárias/etiologia , Hipersensibilidade a Drogas/etiologia , Eritropoetina/administração & dosagem , Humanos , Injeções Intravenosas , Ferro/efeitos adversos , Ferro da Dieta/administração & dosagem , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Proteínas Recombinantes , Diálise RenalRESUMO
OBJECTIVE: To investigate the effect of methylene blue, an inhibitor of oxygen radicals, on lung injury caused by reperfusion of ischemic tissue. METHODS: Intestinal ischemia-reperfusion injury was induced in rats by clamping the superior mesenteric artery for 1 hour. Thereafter, the experimental group was administered 1% methylene blue intraperitoneally and the control group received saline. After 4 hours, pulmonary histopathologic features were assessed, and lung wet-weight to dry-weight ratios and tissue xanthine oxidase were determined. RESULTS: The control group suffered from severe pulmonary parenchymal damage, compared with slight damage in the experimental group. The number of sequestered neutrophils was significantly higher in the control group (319 +/- 60 polymorphonuclear cells per 10 high-power fields) than in the methylene blue-treated group (91 +/- 8 polymorphonuclear cells per 10 high-power fields; p < 0.001). The wet-weight to dry-weight ratio was significantly increased in the saline-treated rats compared with the methylene blue-treated group (6.19 +/- 0.28 vs. 5.07 +/- 0.21; p < 0.001). Xanthine oxidase activity was similar in both groups. CONCLUSION: Methylene blue attenuated lung injury after intestinal ischemia-reperfusion. Inhibition of oxygen free radicals may be the protective mechanism.
Assuntos
Antioxidantes/uso terapêutico , Intestinos/irrigação sanguínea , Azul de Metileno/uso terapêutico , Traumatismo por Reperfusão/complicações , Síndrome do Desconforto Respiratório/tratamento farmacológico , Síndrome do Desconforto Respiratório/etiologia , Animais , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Contagem de Leucócitos , Masculino , Neutrófilos , Tamanho do Órgão , Distribuição Aleatória , Ratos , Ratos Wistar , Síndrome do Desconforto Respiratório/enzimologia , Síndrome do Desconforto Respiratório/imunologia , Síndrome do Desconforto Respiratório/patologia , Xantina Oxidase/análiseRESUMO
BACKGROUND: Rats with chronic renal failure have a low nitric oxide (NO) production and a diminished NO excretion. The supplementation of L-arginine has an inhibitory effect on the progression of renal insufficiency. METHODS: The present study was designed to determine whether chronic renal failure patients have a low NO production. Plasma and urine nitrate (NO3) and nitrite (NO2), stable metabolites of NO, were measured in 83 consecutive patients with chronic renal failure. The 83 chronic renal failure patients were divided into three groups: group 1, mild renal failure (creatinine clearance >60 ml/min/1.73 m2); group 2, moderate renal failure (creatinine clearance >30 <60 ml/min/1.73 m2), and group 3, severe renal failure (creatinine clearance <30 ml/min/1.73 m2). Thirty-three healthy volunteers served as controls. RESULTS: The daily urinary NO excretion was significantly lower in patients with moderate and severe renal failure as compared with those with mild renal failure and normal controls. The lowest values were found in the severe renal failure group. When the 24-hour urinary NO excretion or NO per milligram creatinine and the NO clearance were correlated with the renal function in all patients as a group, these parameters were directly correlated with the creatinine clearance and inversely correlated with the serum creatinine level. The plasma NO concentration was not different between the three chronic renal failure groups, but higher than in the controls. Plasma NO in renal failure patients was not correlated with the creatinine clearance or serum creatinine levels. CONCLUSIONS: Chronic renal failure is a state of NO deficiency. Treatment strategies to increase NO production (L-arginine supplementation or other NO compounds) may prove to be useful in maintaining the renal function and slow the progression of renal disease.
Assuntos
Falência Renal Crônica/metabolismo , Óxido Nítrico/biossíntese , Óxido Nítrico/metabolismo , Idoso , Arginina/metabolismo , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Creatinina/urina , Progressão da Doença , Feminino , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-IdadeRESUMO
Changes in nitric oxide (NO) levels were determined in ischaemic acute renal failure in streptozotocin-induced diabetes mellitus rats. Two weeks after streptozotocin administration and immediately after right nephrectomy, the left renal artery was occluded for 60 min. Similar procedures were carried out in non-diabetic rats. The nitrite (NO2) + nitrate (NO3) levels were measured in plasma and urine. The effects of chronic oral supplementation with L-arginine and an NO synthase inhibitor (N-omega-nitro-L-arginine) were also studied in both diabetic and non-diabetic rats before and after renal artery clamping. The rats with diabetic acute renal failure had a much lower creatinine clearance (90 +/- 22 microliters.min-1. 100g body weight-1, p < 0.005), and higher fractional excretion of sodium (FENa)% (10.90 +/- 4.2, p < 0.001) and protein excretion (2078 +/- 69 micrograms/ml creatinine clearance, p < 0.001) compared with the respective values in the non-diabetic groups (163 +/- 30; 1.46 +/- 86; 453.3 +/- 31). The plasma and urine NO2 + NO3 levels were significantly higher in the untreated diabetic rats compared with the untreated normal rats before ischaemia (p < 0.001). The ischaemic acute renal failure in non-diabetic rats increased the plasma and urinary NO2 + NO3 excretion after ischaemia. The urinary excretion of these metabolites decreased significantly and their plasma levels remained unchanged in the ischaemic diabetic rats. The L-arginine administration resulted in a small but significantly higher creatinine clearance after clamping in the non-diabetic rats. The NO synthase inhibitor caused deterioration in renal function in all ischaemic and non-ischaemic groups. In summary, the greater vulnerability to ischaemia of the diabetic kidney seems to be associated with both impaired response to and impaired production of NO.
Assuntos
Injúria Renal Aguda/fisiopatologia , Diabetes Mellitus Experimental/fisiopatologia , Nefropatias Diabéticas/fisiopatologia , Isquemia/fisiopatologia , Óxido Nítrico/fisiologia , Circulação Renal , Injúria Renal Aguda/sangue , Análise de Variância , Animais , Arginina/farmacologia , Creatinina/metabolismo , Diabetes Mellitus Experimental/sangue , Nefropatias Diabéticas/sangue , Nefrectomia , Nitratos/sangue , Nitratos/urina , Nitritos/sangue , Nitritos/urina , Nitroarginina/farmacologia , Ratos , Ratos Wistar , Valores de Referência , Artéria Renal , Sódio/urinaRESUMO
1. The present study was performed to determine the relationship between diabetic glomerular hyperfiltration and nitric oxide as modulated by the chronic administration of L-arginine and/or N-omega-nitro-L-arginine, a known nitric oxide synthase inhibitor in streptozotocin-induced diabetic rats. 2. Normal rats and rats drinking hypertonic glucose (10%) were used as time-controlled groups. Six weeks after administration of streptozotocin the diabetic rats had significantly higher creatinine clearance (667 +/- 53 microliters min-1 100 g-1 body weight) than before and streptozotocin (456 +/- 38 microliters min-1 100 g-1 body weight, P < 0.005) and very high plasma (37.8 +/- 10.9 mumol/l) and urinary (3.492 +/- 0.179 nmol min-1 100 g-1 body weight) nitrite+nitrate (stable metabolites of nitric oxide) values compared with before streptozotocin administration [19.3 +/- 2.8 mumol/l (P < 0.001) and 0.420 +/- 0.051 nmol min-1 100 g-1 body weight (P < 0.001) respectively]. The 6-week diabetic rats had higher systolic blood pressure (124.2 +/- 2.9 mmHg, P < 0.05) than before streptozotocin (108 +/- 8 mmHg), but had a value similar to that of the hypertonic-glucose-drinking rats. 3. The diabetic rats supplemented with L-arginine did not show an increase in creatinine clearance and had a lower urinary excretion of nitrite+nitrate (0.999 +/- 0.27 nmol min-1 100 g-1 body weight, P < 0.005) than the respective untreated streptozotocin-induced diabetic rats. Creatinine clearance increased in the normal and glucose-drinking rats that received L-arginine. The administration of L-arginine resulted in significant reduction in blood pressure in all groups studied. The chronic nitric oxide synthase inhibitor resulted in high blood pressure, and in a significant decrease in creatinine clearance and urinary nitrite+nitrate excretion in all groups studied. In both diabetic and glucose-drinking rats, the L-arginine therapy resulted in significantly lower plasma and urinary glucose levels than in their respective untreated control groups. 4. The nitric oxide synthase inhibitor increased the plasma and urinary glucose concentration in both diabetic and glucose-drinking rats. 5. Our results indicate that diabetic rats are characterized by high plasma concentrations and elevated urinary excretion of nitrite+nitrate, suggesting a state of high nitric oxide production. The vascular response to nitric oxide in diabetic rats may be different at the glomerular and peripheral vascular bed.
Assuntos
Arginina/farmacologia , Diabetes Mellitus Experimental/metabolismo , Óxido Nítrico/metabolismo , Aloxano , Animais , Arginina/análogos & derivados , Creatina/metabolismo , Taxa de Depuração Metabólica/efeitos dos fármacos , Nitratos/sangue , Nitratos/urina , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico Sintase/antagonistas & inibidores , Nitritos/sangue , Nitritos/urina , Nitroarginina , Ratos , Ratos WistarRESUMO
Iron deficiency may develop in hemodialysis patients, especially when erythropoietin is given. The role of iron deficiency in the anemia of predialysis chronic renal failure (CRF), however, is much less clear. We have intravenously (IV) administered iron as ferric saccharate in a total dose of 200 mg elemental iron monthly for 5 months to 33 CRF patients who remained anemic despite oral iron supplementation and who had no laboratory signs of iron overload. None was receiving erythropoietin therapy. In 22 of the patients there was an increase in the hematocrit values by the end of the study. These patients were considered responders to intravenous iron (IV Fe) therapy. In 11 patients the iron administration was not associated with improvement of the anemia (nonresponders). Before onset of the IV Fe therapy there were no differences between the responders and nonresponders with regard to degree of anemia, serum ferritin, iron saturation, renal function, or blood pressure. One additional patient was excluded from the study because of a mild reaction during an IV test dose before the study. No worsening of kidney function and no other side effects were noted. In four patients (three responders and one nonresponder) the control of blood pressure necessitated antihypertensive drug therapy adjustment. In conclusion, IV Fe supplementation in two thirds of anemic CRF patients not receiving dialysis resulted in a significant improvement of the anemia, thus avoiding the necessity of erythropoietin or blood administration. This could be achieved by increasing the plasma ferritin levels to 200 to 400 microns/L and/or increasing the iron saturation to 25% to 35%. Intravenous ferric saccharate appears to be a safe and effective method of administering iron for the correction of anemia in CRF patients not receiving dialysis.
Assuntos
Anemia Ferropriva/tratamento farmacológico , Compostos Férricos/administração & dosagem , Falência Renal Crônica/complicações , Administração Oral , Adulto , Idoso , Anemia/tratamento farmacológico , Anemia/etiologia , Anemia Ferropriva/etiologia , Preparações de Ação Retardada/administração & dosagem , Eritropoetina , Feminino , Óxido de Ferro Sacarado , Compostos Ferrosos/administração & dosagem , Seguimentos , Ácido Glucárico , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Diálise Renal , Fatores de TempoRESUMO
In the present prospective study we examined the long-term effect of intravenous supplementation with ferric saccharate (IV Fe) in the treatment of the anemia of chronic dialysis patients. All patients, 64 on chronic hemodialysis (HD) and 9 on chronic ambulatory peritoneal dialysis (CAPD), were treated intravenously with this preparation in a dose of 100 mg elemental iron twice monthly. There were five groups. Group 1: 41 HD patients who were receiving erythropoietin (EPO) for at least 6 months prior to the addition of IV Fe. In this group, when IV Fe was given over 6 months, the hematocrit (Hct) increased from a mean of 28.7 to 33.7%. Over the next 6 months, the EPO dose was gradually reduced by a mean of 61.1%, but the mean Hct remained unchanged. Group 2: 11 HD patients who started IV EPO simultaneously with the IV Fe. In this group, over 6 months, the mean Hct increased from 28.1 to 34.1. Over the next 6 months, the EPO dose was gradually reduced by 75.7%, but the mean Hct remained unchanged. Group 3: 12 HD patients who received IV Fe alone for 12 months. The mean Hct increased from 30.5 to 37.9%. Group 4: 4 CAPD patients who had been receiving subcutaneous EPO for at least 6 months prior to IV Fe therapy. Over the subsequent 6 months of IV Fe, the mean Hct increased from 28.4 to 33.3%. Group 5: 5 CAPD patients not on EPO who received IV Fe for 6 months. The mean Hct increased from 27.7 to 35.6%. No adverse effects were seen in any patients throughout the study. In conclusion, adequate Fe supplementation may allow the target Hct of about 33% to be reached without, or with only very low doses of EPO. IV Fe as ferric saccharate is a new and safe form of parenteral iron therapy of the anemia of chronic dialysis patients.
Assuntos
Compostos Férricos/administração & dosagem , Falência Renal Crônica/tratamento farmacológico , Diálise Peritoneal Ambulatorial Contínua , Diálise Renal , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/tratamento farmacológico , Anemia/etiologia , Combinação de Medicamentos , Eritropoetina/uso terapêutico , Feminino , Óxido de Ferro Sacarado , Ferritinas/sangue , Ácido Glucárico , Humanos , Injeções Intravenosas , Ferro/administração & dosagem , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
The effect of oral supplementation of L-arginine, the substrate of nitric oxide, (1.25 g/liter water) and captopril (15 mg/liter water) was studied in 5/6 nephrectomized rats for a period of three months. N-omega-nitro L-arginine, a nitric oxide synthase inhibitor, was given orally (70 mg/liter water) with or without L-arginine or captopril. The urinary excretion of nitrite (NO2) + nitrate (NO3), the known metabolites of nitric oxide, was taken as an index of nitric oxide production. Chronic renal failure rats were characterized by a low creatinine clearance, high FENa%, proteinuria, hypertension and a low urinary excretion of NO2 + NO3; 0.152 +/- 0.06 (P < 0.001) nmol/micrograms creatinine compared with 0.481 +/- 0.004 (P < 0.001) in normal rats and 0.479 +/- 0.11 (P < 0.001) in untreated sham-operated rats. Both L-arginine and captopril were effective in the normalization of all these parameters. The combination of L-arginine and captopril had no additive effects. The nitric oxide synthase inhibitor significantly diminished the captopril beneficial effect. It is concluded that chronic renal failure in rats is a low nitric oxide production state. The supplementation of L-arginine is shown to overcome this condition. It is suggested that the beneficial effect of captopril on chronic renal failure is through a specific L-arginine--nitric oxide synthase--nitric oxide pathway.
Assuntos
Arginina/farmacologia , Captopril/farmacologia , Falência Renal Crônica/prevenção & controle , Óxido Nítrico/biossíntese , Administração Oral , Animais , Pressão Sanguínea/efeitos dos fármacos , Creatinina/metabolismo , Feminino , Masculino , Natriurese/efeitos dos fármacos , Nitratos/urina , Nitritos/urina , Proteinúria/urina , Ratos , Ratos Sprague-DawleyRESUMO
EDRF results from the metabolism of L-arginine. N-omega-nitro-L-arginine is a nitric oxide synthase inhibitor (L-arginine competitive inhibitor). Acute renal failure was induced by i.m glycerol (50%) 5 ml/kg bw. L-arginine: 3 mg/kg bw/min for 60 min before and 60 min after glycerol administration. L-arginine inhibitor (150 micrograms/kg bw/min for 120 min). Cin, Cpah and FENa% were measured immediately or 24 h after glycerol (mean of three periods of 20 min). A second series of similar experiments was done in dehydrated (16 h) rats with a high dose of glycerol (50% solution, 10 ml/kg bw). L-arginine ameliorates the severity of ARF immediately after glycerol administration and enhances the recovery of glycerol-induced ARF. The L-arginine inhibitor resulted in a more severe ARF. Urinary cGMP decreased significantly after glycerol administration. It is concluded that nitric oxide has an important pathogenetic role in the glycerol induced ARF.
Assuntos
Injúria Renal Aguda/etiologia , Glicerol/toxicidade , Óxido Nítrico/fisiologia , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/fisiopatologia , Aminoácido Oxirredutases/antagonistas & inibidores , Animais , Arginina/análogos & derivados , Arginina/antagonistas & inibidores , Arginina/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , GMP Cíclico/urina , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Taxa de Filtração Glomerular/fisiologia , Masculino , Óxido Nítrico Sintase , Nitroarginina , Ratos , Ratos Sprague-Dawley , Circulação Renal/efeitos dos fármacos , Circulação Renal/fisiologiaRESUMO
The hemodynamic effects of the slow release form of a calcium channel blocker, nifedipine retard, in essential hypertension patients after angiotensin II (AII) infusion were studied using nuclear ventriculography. Sublingual nifedipine lowered blood pressure that had been acutely raised by an infusion of AII to its baseline level. When used for 4 weeks, nifedipine retard maintained its blood-pressure-lowering effects without a change in heart rate, both when used alone and when used in addition to beta-adrenergic blockers. In the patients with untreated essential hypertension, nifedipine counteracted the lowering effect of AII on left ventricular ejection fraction (LVEF), which was 67.5 +/- 8.9% at recumbency, 61.2 +/- 6.6% (+/- SD) during AII infusion, and 72.1 +/- 7.5% 30 minutes after sublingual nifedipine. These acute effects seem to result from a marked reduction in total peripheral resistance (TPR) and are accompanied by a rise in cardiac index (CI). The TPR, in dynes/sec/cm-5, was 1376.9 +/- 275.8 at recumbency, 2000.7 +/- 358 during AII infusion, and 1228.6 +/- 289 30 minutes after sublingual nifedipine. The corresponding figures for CI in liters/M2 BSA, were 4.02 +/- 0.77, 3.03 +/- 0.64, and 4.32 +/- 0.79. In patients receiving beta-blocker therapy (propranolol or atenolol) with inadequate control of blood pressure, similar results were obtained in LVEF (69.7 +/- 8.87% at recumbency, 63.7 +/- 11.9% during AII infusion, and 72.2 +/- 6.05% 30 minutes after sublingual nifedipine). The initial TPR was much higher than that of untreated essential hypertensive patients. Nevertheless, the increase obtained during AII infusion was counteracted by sublingual nifedipine. CI was decreased by AII.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Angiotensina II/farmacologia , Hipertensão/tratamento farmacológico , Nifedipino/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Adulto , Pressão Sanguínea/efeitos dos fármacos , Quimioterapia Combinada , Feminino , Frequência Cardíaca/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Sistema Renina-Angiotensina/efeitos dos fármacos , Resistência Vascular/efeitos dos fármacosAssuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Hipertensão/tratamento farmacológico , Bloqueadores dos Canais de Cálcio/efeitos adversos , Bloqueadores dos Canais de Cálcio/farmacologia , Circulação Coronária/efeitos dos fármacos , Quimioterapia Combinada , Humanos , Hipotensão/induzido quimicamente , Metildopa/uso terapêutico , Nifedipino/uso terapêutico , Resistência Vascular/efeitos dos fármacos , Verapamil/uso terapêuticoRESUMO
The immediate antihypertensive effect of 10 mg nifedipine sublingually (nifedipine test), was measured in 19 chronic renal failure hypertensive patients on dialysis and 34 essential hypertensive patients with normal kidney function. The blood pressure decreased significantly in both groups. The minimal values were observed between 30 and 60 minutes after the sublingual administration of nifedipine. The blood pressure decreased from 178 +/- 3.3/104.0 +/- 3.9 to 136.0 +/- 4.7/87.5 +/- 5.1 mm Hg (p less than 0.001) in dialysis patients and from 176.8 +/- 4.5/107.1 +/- 2.4 to 133.0 +/- 3.0/81.7 +/- 2.2 mm Hg in essential hypertension patients (p less than 0.001). The decrease in blood pressure during the test had a significant positive correlation with the pre-test values. Thirteen hypertensive patients on dialysis and 20 essential hypertensive patients completed 2 weeks of daily oral nifedipine therapy, with a dose of 30 to 40 mg per day. The mean blood pressure at the end of the 2 weeks of treatment decreased from 179.5 +/- 4.5/108.5 +/- 5.3 mm Hg to 154.4 +/- 6.3/82.3 +/- 2.6 mm Hg (p less than 0.001) in dialysis patients, and from 176.8 +/- 5.8/110.3 +/- 2.9 to 151.3 +/- 5.3/93.5 +/- 2.6 mm Hg (p less than 0.001) in essential hypertension patients. The present results reveal that nifedipine has a powerful immediate as well as a long-term antihypertensive action in dialysis patients with high blood pressure. This effect is similar to that obtained in essential hypertensive patients.