RESUMEN
OBJECTIVES: To compare maternal flow-mediated dilation (FMD) of the brachial artery and nitrite concentration between third trimester of pregnancy (3rdT) and postpartum (PP) period. Additionally, we will evaluate whether FMD correlates with nitrite concentration in both periods. METHODS: Eligibility criteria was healthy women with singleton pregnancy, gestational age >28 weeks, nonsmokers, and no personal or family history of vascular disease. Each women was examined during 3rdT and between 8 and 12 weeks PP to evaluate FMD and nitrite concentration in whole blood. Women not examined in both periods were excluded. Values between both periods were compared using paired t tests. Correlation between FMD and nitrite was examined by Pearson correlation coefficient. Significance level set as p < 0.05. RESULTS: We invited 42 pregnant women. Among them, 35 were eligible and 7 of them were excluded for not attending the PP evaluation resulting in 28 participants analyzed. We found no significant change in FMD (10.39 ± 5.57% vs. 8.42 ± 4.21%; p = 0.11; 3rdT vs. PP, respectively) and no significant change in nitrite concentration (257.41 ± 122.95 nmol/L vs. 237.16 ± 90.01 nmol/L; p = 0.28). Baseline brachial artery diameter had a significant reduction (3.11 ± 0.30 to 2.75 ± 0.34 mm; p < 0.01). No significant correlation between FMD and nitrite during 3rdT (r = -0.13; p = 0.50) or PP (r = 0.14; p = 0.48) was found. CONCLUSIONS: We did not observe significant changes in both FMD and nitrite concentration between third trimester and the PP period. FMD did not correlate with nitrite in both periods. More studies are needed to confirm our findings.
Asunto(s)
Endotelio Vascular/fisiología , Nitritos/sangre , Periodo Posparto/fisiología , Tercer Trimestre del Embarazo/fisiología , Embarazo/fisiología , Adolescente , Adulto , Femenino , Humanos , Estudios Prospectivos , Vasodilatación , Adulto JovenRESUMEN
Erectile dysfunction (ED) is a multifactorial disease associated with vascular dysfunction, low nitric oxide (NO) bioavailability, and oxidative stress. However, it is not known whether low NO bioavailability and oxidative stress affect the responsiveness of ED patients to sildenafil. We tested this hypothesis by studying 28 healthy subjects (control group), 26 patients with ED without comorbidities (ED group), and 18 patients with ED and diabetes mellitus (ED/DM group). The International Index for Erectile Function (IIEF) questionnaire was used to assess the erectile function of all participants, and their responsiveness to sildenafil was assessed as the percentage of change in the five-item version of IIEF score before and after sildenafil treatment. Levels of whole blood nitrite, antioxidants markers (ferric reducing ability of plasma (FRAP) and reduced glutathione), and oxidative stress markers (thiobarbituric acid reactive substance and protein carbonyl) were determined. We found a negative correlation between whole blood nitrite levels and the responses to sildenafil in both ED groups (P<0.05). FRAP correlated negatively with the responses to sildenafil in the ED/DM group (P<0.05). No other significant associations were found. Our findings show evidence that low NO bioavailability is associated with better responses to sildenafil in patients with ED (with or without DM).
Asunto(s)
Disfunción Eréctil/metabolismo , Óxido Nítrico/metabolismo , Nitritos/sangre , Inhibidores de Fosfodiesterasa 5/farmacología , Piperazinas/farmacología , Sulfonas/farmacología , Adulto , Anciano , Disponibilidad Biológica , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Disfunción Eréctil/tratamiento farmacológico , Glutatión/sangre , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de Fosfodiesterasa 5/uso terapéutico , Piperazinas/uso terapéutico , Carbonilación Proteica , Purinas/farmacología , Purinas/uso terapéutico , Citrato de Sildenafil , Sulfonas/uso terapéutico , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Resultado del TratamientoRESUMEN
PURPOSE: The antihypertensive effects of angiotensin-converting enzyme inhibitors (ACEi) are explained, at least in part, by enhanced bradykinin-dependent nitric oxide (NO) formation and decreased angiotensin II-induced oxidative stress and vasoconstriction. We examined for the first time whether treatment with enalapril increases the plasma levels of markers of NO formation and decreases oxidative stress in mild to moderate hypertensive patients. METHODS: Eighteen untreated hypertensive patients were treated with enalapril 10 mg/day (n=10) or 20 mg/day (n=8) for 60 days. Eighteen normotensive healthy controls were followed for the same period. Venous blood samples were collected at baseline and after 30/60 days of treatment with enalapril. Plasma NOx (nitrites + nitrates) concentrations were determined by using the Griess reaction. Plasma nitrite and whole blood nitrite concentrations were determined by using an ozone-based chemiluminescence assay. Plasma thiobarbituric acid-reactive species (TBARS) and 8-isoprostane concentrations were determined by a fluorimetric method and by ELISA, respectively. RESULTS: Treatment with enalapril decreased blood pressure in hypertensive patients. However, we found no significant changes in plasma NOx, nitrite, whole blood nitrite, and in the levels of markers of oxidative stress in both normotensive controls and hypertensive patients treated with enalapril. CONCLUSIONS: Our data show that enalapril 10-20 mg/day does not affect the concentrations of relevant markers of NO formation or markers of oxidative stress in mild to moderately hypertensive subjects, despite satisfactory blood pressure control. Our findings do not rule out the possibility that ACEi may produce such effects in more severely hypertensive patients treated with higher doses of ACEi.
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Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Enalapril/farmacología , Enalapril/uso terapéutico , Hipertensión/tratamiento farmacológico , Óxido Nítrico/metabolismo , Adulto , Biomarcadores Farmacológicos/sangre , Presión Sanguínea/efectos de los fármacos , Dinoprost/análogos & derivados , Dinoprost/sangre , Humanos , Hipertensión/diagnóstico , Persona de Mediana Edad , Nitratos/sangre , Nitritos/sangre , Estrés Oxidativo/efectos de los fármacos , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
Contrasting with increased nitric oxide (NO) formation during healthy pregnancy, reduced NO bioavailability plays a role in preeclampsia. However, no study has examined whether increased NO consumption by enhanced circulating levels of cell-free hemoglobin plays a role in preeclampsia. We studied 82 pregnant women (38 healthy pregnant and 44 with preeclampsia). To assess NO bioavailability, we measured plasma and whole blood nitrite concentrations using an ozone-based chemiluminescence assay. Plasma ceruloplasmin concentrations and plasma NO consumption (pNOc) were assessed and plasma hemoglobin (pHb) concentrations were measured with a commercial immunoassay. We found lower whole blood and plasma nitrite concentrations in preeclamptic patients (-48 and -39%, respectively; both P<0.05) compared with healthy pregnant women. Plasma samples from preeclamptic women consumed 63% more NO (P=0.003) and had 53% higher pHb and 10% higher ceruloplasmin levels than those found in healthy pregnant women (P<0.01). We found significant positive correlations between pHb and pNOc (r=0.61; P<0.0001), negative correlations between pNOc and whole blood or plasma nitrite concentrations (P=0.02; r=-0.32 and P=0.01; r=-0.34, respectively), and negative correlations between pHb and whole blood or plasma nitrite concentrations (P=0.03; r=-0.36 and P=0.01; r=-0.38, respectively). These findings suggest that increased pHb levels lead to increased NO consumption and lower NO bioavailability in preeclamptic compared with healthy pregnant women.
Asunto(s)
Hemoglobinas/metabolismo , Óxido Nítrico/farmacocinética , Preeclampsia/sangre , Adulto , Disponibilidad Biológica , Ceruloplasmina/análisis , Femenino , Humanos , Óxido Nítrico/sangre , Nitritos/sangre , Embarazo , ProhibitinasRESUMEN
Nitric oxide (NO) is a major regulator of the cardiovascular system. However, the effects of endothelial nitric oxide synthase (eNOS) gene polymorphisms or haplotypes on the circulating concentrations of nitrite (a sensitive marker of NO formation) and cGMP are unknown. Here we examined the effects of eNOS polymorphisms in the promoter region (T-786C), in exon 7 (Glu298Asp), and in intron 4 (4b/4a) and eNOS haplotypes on the plasma levels of nitrite and cGMP. We hypothesized that eNOS haplotypes could have a major impact on NO formation. We genotyped 142 healthy subjects by PCR-RFLP. To assess NO formation, the plasma concentrations of nitrite and cGMP were determined using an ozone-based chemiluminescence assay and an enzyme immunoassay. Haplotypes were inferred using the PHASE 2.1 program. No significant differences were found in age, body mass index, systolic and diastolic arterial blood pressure, heart rate, total cholesterol, triglycerides, cGMP, or nitrite among the genotype groups for the three polymorphisms studied here (all p>0.05). Interestingly, the C-4b-Glu haplotype was associated with lower plasma nitrite concentrations than those found in the other haplotype groups (p<0.05), but not with different cGMP levels (p>0.05). These findings suggest that eNOS gene variants combined within a specific haplotype modulate NO formation, although individual eNOS polymorphisms probably do not have major effects.
Asunto(s)
Óxido Nítrico Sintasa de Tipo III/genética , Óxido Nítrico/biosíntesis , Adolescente , Adulto , GMP Cíclico/sangre , Femenino , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Óxido Nítrico Sintasa de Tipo III/metabolismo , Nitritos/sangre , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de RestricciónRESUMEN
Statins inhibit cholesterol synthesis and produce pleiotropic, cholesterol-independent effects including endothelial NO synthase (eNOS) stimulation and increased expression. However, a functional polymorphism in the promoter of the eNOS gene (T-786C) reduces its activity and could modulate the response to statins. Here, we examined whether this polymorphism modulates the effects of atorvastatin on the plasma levels of markers of NO formation and oxidative stress. We genotyped 200 healthy subjects for this polymorphism, and 15 subjects with the TT genotype and 15 with the CC genotype were selected to receive placebo or atorvastatin 10 mg/day po for 14 days. To assess NO bioavailability, the plasma concentrations of nitrate, nitrite, and cGMP and the whole blood nitrite concentrations were determined after placebo or atorvastatin using an ozone-based chemiluminescence assay and an enzyme immunoassay. Thiobarbituric acid-reactive species (TBA-RS) were measured in the plasma to assess oxidative stress. Atorvastatin decreased cholesterol concentrations independent of genotype. Whereas atorvastatin produced no significant changes in plasma nitrite, nitrate, or cGMP concentrations in both genotype groups, atorvastatin increased whole blood nitrite concentrations and decreased plasma TBA-RS concentrations in the CC (but not in the TT) genotype group. These findings suggest that the T-786C polymorphism modulates the effects of atorvastatin on NO bioavailability and oxidative stress.
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Ácidos Heptanoicos/farmacología , Óxido Nítrico Sintasa de Tipo III/genética , Óxido Nítrico Sintasa de Tipo III/metabolismo , Nitritos/sangre , Polimorfismo Genético/genética , Pirroles/farmacología , Adolescente , Adulto , Sustitución de Aminoácidos , Atorvastatina , GMP Cíclico/sangre , Humanos , Masculino , Malondialdehído/sangre , Persona de Mediana Edad , TiobarbitúricosRESUMEN
Lead exposure has been associated with increased cardiovascular risk, which may result, at least in part, from lead-induced increases in oxidative stress and depressed nitric oxide (NO) availability. However, no previous clinical study has examined whether lead exposure is associated with significant effects on biomarkers of NO activity (plasma nitrites, nitrates, and cyclic guanosine 3',5'-monophosphate; cGMP). We investigated whether there is an association between the circulating concentrations of nitrites, nitrates, and cGMP and the concentrations of lead in whole blood (B-Pb) or plasma (P-Pb) from 62 lead-exposed subjects (30 men and 32 women). P-Pb was determined by inductively coupled plasma mass spectrometry and B-Pb by graphite furnace atomic absorption spectrometry. Plasma nitrite and nitrate concentrations were measured using an ozone-based chemiluminescence assay. Plasma cGMP concentrations were measured using a commercial enzyme immunoassay. We found a negative correlation between plasma nitrite and B-Pb concentrations (r = -0.358; P = 0.004), and between plasma nitrite and P-Pb concentrations (r = -0.264; P = 0.038), thus suggesting increased inhibition of NO formation with increasing B-Pb or P-Pb concentrations. However, no significant correlations were found between plasma nitrate or cGMP and B-Pb or P-Pb concentrations (all P > 0.05). These findings suggest a significant inhibitory effect of lead exposure on NO formation and provide clinical evidence for a biological mechanism possibly involved the association between lead exposure and increased cardiovascular risk.