RESUMO
Nitric oxide (NO) contributes to maintaining normal cardiovascular and renal function. This bioactive signalling molecule is generally formed enzymatically by NO synthase in the vascular endothelium. NO bioactivity can also be attributed to dietary intake of inorganic nitrate, which is abundant in our diet, especially in green leafy vegetables and beets. Ingested nitrate is reduced to nitrite by oral commensal bacteria and further to NO systemically. Previous studies have shown that dialysis, by means of removing nitrate and nitrite from the body, can reduce NO bioactivity. Hence, dietary intervention approaches aimed to boost the nitrate-nitrite-NO pathway may be of benefit in dialysis patients. The purpose of this study was to examine the kinetics of plasma nitrate and nitrite after a single intake of nitrate-rich concentrated beetroot juice (BJ) in adult hemodialysis (HD) patients and in age-matched healthy volunteers (HV). Eight HD patients and seven HV participated in this single center, randomized, single-blind, placebo-controlled, crossover study. Each participant received a sequential single administration of active BJ (70 mL, 400 mg nitrate) and placebo BJ (70 mL, 0 mg nitrate) in a random order separated by a washout period of seven days. For the kinetic analysis, blood samples were collected at different time-points before and up to 44 h after BJ intake. Compared with placebo, active BJ significantly increased plasma nitrate and nitrite levels both in HD patients and HV. The area under the curve and the maximal concentration of plasma nitrate, but not of nitrite, were significantly higher in HD patients as compared with HV. In both groups, active BJ ingestion did not affect blood pressure or plasma potassium levels. Both BJs were well tolerated in all participants with no adverse events reported. Our data provide useful information in planning dietary nitrate supplementation efficacy studies in patients with reduced NO bioactivity.
Assuntos
Beta vulgaris , Nitritos , Adulto , Antioxidantes/análise , Pressão Sanguínea , Estudos Cross-Over , Suplementos Nutricionais , Sucos de Frutas e Vegetais/análise , Humanos , Cinética , Nitratos , Óxido Nítrico/metabolismo , Diálise Renal , Método Simples-CegoRESUMO
BACKGROUND & PURPOSE: It is well established that end-stage renal disease (ESRD) is associated with increased cardiovascular morbidity and mortality both in the adult and pediatric population. Although the underlying molecular mechanisms are poorly understood, compromised nitric oxide (NO) bioactivity has been suggested as a contributing factor. With this in mind, we investigated the effects of hemodialysis on NO homeostasis and bioactivity in blood. METHODS & RESULTS: Plasma and dialysate samples were obtained before and after hemodialysis sessions from adults (n = 33) and pediatric patients (n = 10) with ESRD on chronic renal replacement therapy, and from critically ill adults with acute kidney injury (n = 12) at their first sustained low-efficiency dialysis session. Levels of nitrate, nitrite, cyclic guanosine monophosphate (cGMP) and amino acids relevant for NO homeostasis were analyzed. We consistently found that nitrate and cGMP levels in plasma were significantly reduced after hemodialysis, whereas post-dialysis nitrite and amino acids coupled to NO synthase activity (i.e., arginine and citrulline) were only significantly reduced in adults with ESRD. The amount of excreted nitrate and nitrite during dialysis were similar to daily endogenous levels that would be expected from endothelial NO synthase activity. CONCLUSIONS: Our results show that hemodialysis significantly reduces circulating levels of nitrate and cGMP, indicating that this medical procedure may impair NO synthesis and potentially NO signaling pathways.
Assuntos
Injúria Renal Aguda/terapia , Falência Renal Crônica/terapia , Nitratos/isolamento & purificação , Nitritos/isolamento & purificação , Diálise Renal , Injúria Renal Aguda/sangue , Adulto , Criança , Estudos Transversais , Feminino , Humanos , Falência Renal Crônica/sangue , Masculino , Nitratos/sangue , Nitritos/sangue , Estudos ProspectivosRESUMO
AIMS: To test whether blood pressure is affected by potassium supplementation which modifies urinary kallikrein (UK) in SHR of either sex, and to elucidate the mechanisms involved. DESIGN: In SHR and WKY blood pressure, renal function and hormonal profile were studied after 1% oral potassium supplementation starting at 4 weeks of age and throughout until 12 weeks of age. Results were compared with those of untreated SHR and WKY of either sex. RESULTS: Systolic blood pressure (mm Hg) started to rise in SHR and was significantly different at 6-8 weeks of age: 153.5 +/- 7.9 versus 100 +/- 5.6 in female and 157 +/- 7.7 versus 98.4 +/- 6.8 in male rats (p < 0.01). Systolic blood pressure increased progressively in female and male rats reaching 164.5 +/- 4.8 and 204.5 +/- 7.6, respectively, at 12 weeks of age. At this time systolic blood pressure was higher in male than in female SHR (p < 0.01) and UK activity (UKa; nkat/day/100 g body weight) was slightly lower in male SHR. After 1% oral potassium supplementation administered from 4 to 12 weeks of age, a decrease in systolic blood pressure was seen in male SHR: 204.5 +/- 7.6 versus 173.5 +/- 7.9 (p < 0.05); and 164.5 +/- 4.8 versus 156.8 +/- 5.5 in female rats (NS) at 12 weeks of age, concomitant with an increase in UKa, particularly in male rats (29.35 +/- 1.92 versus 36.54 +/- 2.61, p < 0.05). As expected, plasma aldosterone (pg/ml), increased markedly after potassium treatment from 129 +/- 31.4 in untreated female and male SHR and WKY to 528 +/- 180.7 in SHR and 473 +/- 88.4 in WKY (p < 0.05 in both cases). After potassium supplementation, potassium excretion was significantly correlated with both aldosterone levels and UKa (p < 0.001 in both cases). No significantly concurrent changes in plasma renin activity were observed, but instead a significant decrease was seen in SHR (p < 0.01). The potassium blood pressure-lowering effect was blunted by aldosterone receptor antagonist treatment that also decreased UKa from 36.5 +/- 2.61 to 19.5 +/- 1.9, particularly in male SHR. No attempt was made in this experimental setting to block kallikrein or kinin receptors. CONCLUSIONS: UKa increases as a consequence of aldosterone stimulation by potassium load since an aldosterone receptor blockade abolishes UKa increment and blood pressure fall. These results further support the hypothesis that the kallikrein kinin system plays a role in blood pressure regulation and they also show a gender different response to potassium load in relation to UKa and blood pressure.
Assuntos
Aldosterona/sangue , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Calicreínas/urina , Potássio na Dieta/administração & dosagem , Potássio na Dieta/metabolismo , Animais , Feminino , Masculino , Ratos , Ratos Endogâmicos SHR , Fatores Sexuais , Resultado do TratamentoRESUMO
While 24-h ambulatory blood pressure monitoring (ABPM) is an established tool for monitoring antihypertensive therapy in adults, data in children are scarce. We retrospectively analysed whether office blood pressure (BP) is reliable for the diagnosis of BP control in 26 treated hypertensive paediatric renal transplants. Controlled office BP was defined as the mean of three replicate systolic and diastolic BP recordings less than or equal to the 95th age-, sex- and height-matched percentile on the three-outpatient visits closest to ABPM. Controlled ABPM was defined as systolic and diastolic daytime BP < or =95th distribution adjusted height- and sex-related percentile of the adapted ABPM reference. Eight recipients (30%) with controlled office BP were in fact categorized as having non-controlled BP by ABPM criteria. Overall, when office BP and ABPM were compared using the Bland and Altman method, the 95% limits of agreement between office and daytime values ranged from -12.6 to 34.1 mmHg for systolic and -23.9 to 31.7 mmHg for diastolic BP, and the mean difference was 10.7 and 3.9 mmHg respectively. Office readings miss a substantial number of recipients who are hypertensive by ABPM criteria. Undertreatment of hypertension could be avoided if ABPM is applied as an adjunct to office readings.
Assuntos
Monitorização Ambulatorial da Pressão Arterial , Hipertensão/tratamento farmacológico , Transplante de Rim/efeitos adversos , Adolescente , Anti-Hipertensivos/uso terapêutico , Determinação da Pressão Arterial , Índice de Massa Corporal , Criança , Ritmo Circadiano , Feminino , Humanos , Transplante de Rim/fisiologia , Masculino , Estudos Retrospectivos , Doadores de Tecidos/estatística & dados numéricosRESUMO
It has been suggested that an abnormal activity of the hypothalamic-pituitary-adrenal-gonadal axis may be implicated in the pathogenesis of spontaneously hypertensive rats (SHR) blood pressure hypertension. However, it is widely known that the kallikrein-kinin system plays a role in blood pressure regulation in this strain, because an inverse relation between blood pressure and urinary kallikrein excretion has been reported. It was of our interest to study how early suppression of sexual hormones affected blood pressure regulation in SHR and urinary kallikrein excretion and to elucidate the involved mechanisms. For these purpose, SH and Wistar-Kyoto (WKY) rats blood pressure, renal function, and hormonal profile were studied after prepuberal gonadectomy starting at 4 weeks of age throughout until the 12th week of age. Results were compared with those of untreated SH and WKY rats of either sex. The response to blocking agents against aldosterone and kallikrein-kinin system also were evaluated. Systolic blood pressure increased progressively in male and female SHR 12 weeks of age. Systolic blood pressure was higher in male than in female SHR, but urinary kallikrein was lower in male SHR. Prepuberal gonadectomy induced a significant decrease in systolic blood pressure in male and in female SHR at 12 weeks of age, accompanied by an increase in urinary kallikrein in male and in female SHR. Plasma aldosterone increased markedly in female and male SHR after gonadectomy. No concurrent changes in plasma renin activity or corticosterone levels were observed. The aldosterone receptor antagonist and the kallikrein inhibitor treatment blunted the blood pressure lowering effect of gonadectomy and diminished urinary kallikrein excretion. Results support the existence of a sexual dimorphism related to hypertension and urinary kallikrein and suggest an interaction among the kallikrein-kinin system, sexual hormones, and mineralocorticoids in the neonatal programming of hypertension.
Assuntos
Aldosterona/sangue , Pressão Sanguínea/fisiologia , Castração , Hipertensão/fisiopatologia , Sistema Calicreína-Cinina/fisiologia , Envelhecimento , Animais , Biomarcadores/sangue , Biomarcadores/urina , Modelos Animais de Doenças , Progressão da Doença , Feminino , Hipertensão/sangue , Hipertensão/urina , Calicreínas/urina , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKYRESUMO
Cyclosporin (CsA) therapy is associated with side effects such as hypertension, hyperlipidemia and nephrotoxicity. Tacrolimus (Tac) has been shown to be more favourable in this respect. We retrospectively analysed office blood pressure (BP), serum total cholesterol (TC) and fasting glucose levels, and estimated graft function profiles in paediatric (n =56) and young adult (n =14) renal transplant recipients whose maintenance immunosuppressive regimen was based upon CsA (n =38) or Tac (n =32) given with mycophenolate mofetil and corticosteroids. The analysis was performed at four different time-points: at 1, 6, 12, and 24 months post-transplant, respectively. Baseline characteristics were comparable between treatment groups. Differences for both systolic and diastolic BP, and graft function between treatment groups became significant from month 1 and throughout the 2-year period. Values (mean +/- SD) for CsA-treated and Tac-treated recipients at 2 years were 118.8+/-11.1 / 74.6+/-7.4 mmHg vs 109.3+/-11.2 / 67.2+/-7.8 mmHg for systolic and diastolic BP, respectively, p <0.005/0.005; and 72.0+/-18.5 ml/min vs 84.0+/-22.4 ml/min per 1.73 m(2) for graft function, respectively, p <0.01. Office hypertension, defined as the use of antihypertensive medication at month 24, was significantly associated with CsA-therapy (chi(2), p <0.01). TC levels became significantly lower at months 6, 12, and 24 in the Tac group compared with the CsA group. Hypercholesterolemia, defined as TC>or=200 mg/dl, was significantly associated with CsA-based immunosuppressive regimen at months 6, 12, and 24 post-transplant (chi(2), p <0.05, p <0.001, and p <0.01, respectively). Although Tac therapy was associated with higher glucose levels, no recipient developed post-transplant diabetes mellitus. The number of recipients who experienced acute rejections was comparable in both groups. In conclusion, Tac-based immunosuppressive therapy was found to be associated with more favourable potential risk-factor profiles for cardiovascular disease and better graft function at 2 years post-transplant compared with CsA-therapy.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/etiologia , Colesterol/sangue , Ciclosporina/farmacologia , Imunossupressores/farmacologia , Transplante de Rim/efeitos adversos , Tacrolimo/farmacologia , Adolescente , Adulto , Glicemia/análise , Criança , Pré-Escolar , Ciclosporina/efeitos adversos , Jejum , Feminino , Humanos , Imunossupressores/efeitos adversos , Lactente , Transplante de Rim/fisiologia , Masculino , Estudos Retrospectivos , Tacrolimo/efeitos adversos , Fatores de TempoRESUMO
Twenty-four-hour ambulatory blood pressure monitoring (ABPM) has proven to have better reproducibility than office blood pressure (BP) and is increasingly used for the study of hypertension in children and adolescents. The aim of our study was to assess 24-h BP profiles and to compare the results of office BP measurements with ABPM in stable liver transplant recipients transplanted before the age of 18 yr. ABPM was performed in 29 patients (nine males, 20 females), aged 3.9-24.8 yr (median 10.8 yr). The investigation was conducted 1.1-11.5 yr (median 5.1 yr) following transplantation. ABPM confirmed hypertension in one out of three office hypertensive patients. Seven patients (24%), whose office BP recordings were within the normotensive range, were reclassified as hypertensive. Non-dippers (n = 17), arbitrarily defined as patients with less than 10% nocturnal fall in BP, were similarly distributed among patients with ambulatory normotension and ambulatory hypertension (chi(2), p = 0.79). In addition, non-dippers showed a negative correlation between 24-h total urinary albumin excretion and both systolic and diastolic nocturnal decline in BP (Rho = -0.48, p < 0.05 and Rho = -0.86, p < 0.01, respectively). Our study found office BP readings to be poorly representative of 24-h BP profile. Larger studies are needed to confirm our observations as well as to determine whether routine BP measurements in the follow-up of paediatric liver transplant recipients should be based solely on office BP.
Assuntos
Monitorização Ambulatorial da Pressão Arterial/métodos , Pressão Sanguínea/fisiologia , Transplante de Fígado , Adolescente , Adulto , Assistência Ambulatorial , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pacientes Ambulatoriais , Cuidados Pós-Operatórios , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de TempoRESUMO
BACKGROUND: In adults, a siesta yields a blood pressure profile similar to that seen in nocturnal sleep. It is therefore stressed that siestas should not be included in daytime blood pressure measurement. OBJECTIVES: To evaluate blood pressure profiles in pediatric and adolescent patients who reported a siesta during 24 h ambulatory blood pressure monitoring (ABPM). METHODS: Patients' diaries of actual sleep times were used to determine the periods of sleep (night-time and siesta) and daytime wakefulness. Ambulatory systolic and/or diastolic daytime and/or night-time hypertension was determined by comparing patients' measurements with normal values taken from published standards for healthy children and adolescents. Data obtained from 12 patients with ambulatory normotension and 12 patients with ambulatory hypertension, who were referred for an evaluation of hypertension or management of known hypertension, were analysed separately. RESULTS: Mean systolic (SBP) and diastolic (DBP) blood pressure values during the daytime awake period were significantly higher than the mean values for the period of daytime, including the siesta, both in patients with ambulatory normotension and in those with ambulatory hypertension (P<0.001 and P<0.01 for SBP and DBP, and P<0.001 and P<0.001 for SBP and DBP, respectively). The percentage night-time falls in SBP and DBP were 12.9+/-0.5 and 19.1+/-1.4 in patients with ambulatory normotension, and 7.1+/-1.5 and 12.9+/-2.2 in patients with ambulatory hypertension. These values were significantly higher when the siesta was excluded from the analysis in both groups (13.9+/-0.5% and 20.7+/-1.5%, P<0.001 and P<0.01 for SBP and DBP in patients with ambulatory normotension; 8+/-1.6% and 14.8+/-2.4%, P<0.001 and P<0.001 for SBP and DBP in patients with ambulatory hypertension, respectively). CONCLUSIONS: By ignoring the effect of the siesta, both the calculation of daytime blood pressure values and the analysis of day-night variability in children and adolescents undergoing ABPM may be erroneously interpreted.