Nitric oxide, cholesterol oxides and endothelium-dependent vasodilation in plasma of patients with essential hypertension

The objective of the present study was to identify disturbances of nitric oxide radical (ANO) metabolism and the formation of cholesterol oxidation products in human essential hypertension. The concentrations ofANO derivatives (nitrite, nitrate, S-nitrosothiols and nitrotyrosine), water and lipid-soluble antioxidants and cholesterol oxides were measured in plasma of 11 patients with mild essential hypertension (H: 57.8 ± 9.7 years; blood pressure, 148.3 ± 24.8/90.8 ± 10.2 mmHg) and in 11 healthy subjects (N: 48.4 ± 7.0 years; blood pressure, 119.4 ± 9.4/75.0 ± 8.0 mmHg).Nitrite, nitrate and S-nitrosothiols were measured by chemiluminescence and nitrotyrosine was determined by ELISA. Antioxidants were determined by reverse-phase HPLC and cholesterol oxides by gas chromatography. Hypertensive patients had reduced endothelium-dependent vasodilation in response to reactive hyperemia (H: 9.3 and N: 15.1 percent increase of diameter 90 s after hyperemia), and lower levels of ascorbate (H: 29.2 ± 26.0, N: 54.2 ± 24.9 æM), urate (H: 108.5 ± 18.9, N: 156.4 ± 26.3 æM), ß-carotene (H: 1.1 ± 0.8, N: 2.5 ± 1.2 nmol/mg cholesterol), and lycopene (H: 0.4 ± 0.2, N: 0.7 ± 0.2 nmol/mg cholesterol), in plasma, compared to normotensive subjects. The content of 7-ketocholesterol, 5alpha-cholestane-3ß,5,6ß-triol and 5,6alpha-epoxy-5alpha-cholestan-3alpha-ol in LDL, and the concentration of endothelin-1 (H: 0.9 ± 0.2, N: 0.7 ± 0.1 ng/ml) in plasma were increased in hypertensive patients. No differences were found for ANO derivatives between groups. These data suggest that an increase in cholesterol oxidation is associated with endothelium dysfunction in essential hypertension and oxidative stress, although ANO metabolite levels in plasma are not modified in the presence of elevated cholesterol oxides

Improved glycemic control by acarbose therapy in hypertensive diabetic patients: effects on blood pressure and hormonal parameters

A double-blind, randomized, placebo-controlled study was carried out on 44 hypertensive type 2 diabetic subjects previously treated by diet associated or not with sulfonylurea to assess the effects of acarbose-induced glycemic control on blood pressure (BP) and hormonal parameters. Before randomization and after a 22-week treatment period (100 to 300 mg/day), the subjects were submitted to a standard meal test and to 24-h ambulatory BP monitoring (ABPM) and had plasma glucose, glycosylated hemoglobin, lipid profile, insulin, proinsulin and leptin levels determined. Weight loss was found only in the acarbose-treated group (75.1 ± 11.6 to 73.1 ± 11.6 kg, P<0.01). Glycosylated hemoglobin decreased only in the acarbose group (6.4 ± 1.7 to 5.6 ± 1.9 percent, P<0.05). Fasting proinsulin decreased only in the acarbose group (23.4 ± 19.3 to 14.3 ± 13.6 pmol/l, P<0.05), while leptin decreased in both (placebo group: 26.3 ± 6.1 to 23.3 ± 9.4 and acarbose group: 25.0 ± 5.5 to 22.7 ± 7.9 ng/ml, P<0.05). When the subset of acarbose-treated patients who improved glycemic control was considered, significant reductions in diurnal systolic, diastolic and mean BP (102.3 ± 6.0 to 99.0 ± 6.6 mmHg, P<0.05) were found. Acarbose monotherapy or combined with sulfonylurea was effective in improving glycemic control in hypertensive diabetic patients. Acarbose-induced improvement in metabolic control may reduce BP in these patients. Our data did not suggest a direct action of acarbose on insulin resistance or leptin levels

Relationship between microalbuminuria and cardiac structural changes in mild hypertensive patients

The aim of this study was to determine the relationship between urinary albumin excretion (UAE), cardiac structural changes upon echocardiography and 24-h ambulatory blood pressure (ABPM) levels. Twenty mild hypertensive patients (mean age 56.8 ± 9.6 years) were evaluated. After 2 weeks of a washout period of all antihypertensive drugs, all patients underwent an echocardiographic evaluation, a 24-h ABPM and an overnight urine collection. Systolic and diastolic blood pressure during 24-h ABPM was 145 ± 14/91 ± 10 mmHg (daytime) and 130 ± 14/76 ± 8 mmHg (nighttime), respectively. Seven (35 percent) patients presented UAE > or = 15 æg/min, and for the whole group, the geometric mean value for UAE was 10.2 x/÷ 3.86 æg/min. Cardiac measurements showed mean values of interventricular septum thickness (IVS) of 11 ± 2.3 mm, left ventricular posterior wall thickness (PWT) of 10 ± 2.0 mm, left ventricular mass (LVM) of 165 ± 52 g, and left ventricular mass index (LVMI) of 99 ± 31 g/m². A forward stepwise regression model indicated that blood pressure levels did not influence UAE. Significant correlations were observed between UAE and cardiac structural parameters such as IVS (r = 0.71, P<0.001), PWT (r = 0.64, P<0.005), LVM (r = 0.65, P<0.005) and LVMI (r = 0.57, P<0.01). Compared with normoalbuminuric patients, those who had microalbuminuria presented higher values of all cardiac parameters measured. The predictive positive and negative values of UAE > or = 15 æg/min for the presence of geometric cardiac abnormalities were 75 and 91.6 percent. These data indicate that microalbuminuria in essential hypertension represents an early marker of cardiac structural damage

Intima-media thickness evaluation by B-mode ultrasound: Correlation with blood pressure levels and cardiac structures

The aim of this study was to analyze the thickness of the intima-media complex (IMC) using a noninvasive method. The carotid and femoral common arteries were evaluated by noninvasive B-mode ultrasound in 63 normotensive and in 52 hypertensive subjects and the thickness of the IMC was tested for correlation with blood pressure, cardiac structures and several clinical and biological parameters. The IMC was thicker in hypertensive than in normotensive subjects (0.67 ± 0.13 and 0.62 ± 0.16 vs 0.54 ± 0.09 and 0.52 ± 0.11 mm, respectively, P<0.0001). In normotensive patients, the simple linear regression showed significant correlations between IMC and age, body mass index and 24-h systolic blood pressure for both the carotid and femoral arteries. In hypertensives the carotid IMC was correlated with age and 24-h systolic blood pressure while femoral IMC was correlated only with 24-h diastolic blood pressure. Forward stepwise regression showed that age, body mass index and 24-h systolic blood pressure influenced the carotid IMC relationship (r2 = 0.39) in normotensives. On the other hand, the femoral IMC relationship was influenced by 24-h systolic blood pressure and age (r2 = 0.40). In hypertensives, age and 24-h systolic blood pressure were the most important determinants of carotid IMC (r2 = 0.37), while femoral IMC was influenced only by 24-h diastolic blood pressure (r2 = 0.10). There was an association between carotid IMC and echocardiographic findings in normotensives, while in hypertensives only the left posterior wall and interventricular septum were associated with femoral IMC. We conclude that age and blood pressure influence the intima-media thickness, while echocardiographic changes are associated with the IMC

Lipid peroxidation and antioxidants in hyperlipidemia and hypertension

Lipid peroxidation and lipid-derived oxidized products have been implicated in the pathogenesis of a variety of human diseases. To clarify the role of oxidative stress in essential hypertension and hypercholesterolemia the in vitro oxidative susceptibility of LDL, the antioxidant status and the lipid peroxide content of blood plasma were examined in hypercholesterolemic (HC), hypertensive (H), hypercholesterolemic/hypertensive (HH) and normolipidemic/normotensive subjects (N). Plasma ascorbate and lipid-soluble antioxidants were lower, while LDL oxidizability, CE-OOH and TL-OOH were higher in H, HC, and HH groups than in the N group. No difference was observed among groups for PL-OOH and isoprostanes. In summary, the results show that: 1) lipid- and water-soluble antioxidants are lower in hypercholesterolemic and hypertensive patients as compared to normal subjects, whereas the lipid peroxide content and the LDL susceptibility to oxidation were higher; 2) total cholesterol, LDL-cholesterol, apoB and CE-OOH were negatively correlated with the content of a-tocopherol; 3) there was a positive correlation between the content of lipid-soluble antioxidants and the resistance of LDL to oxidation; and 4) CE-OOH and TL-OOH were positively correlated with total cholesterol and LDL-cholesterol.

Abnormal nocturnal blood pressure fall in normmotensive adolescents with insulin-dependent diabetes is ameliorated following glycemic improvement

Lack of the physiological nocturnal fall in blood pressure (BP) has been found in diabetics an it seems to be related to the presence of diabetic complications. The present study examined the changes in the nocturnal BP pattern of 8 normotensive insulin-dependent diabetic adolescents without nephropathy following improvement in glycemic control induced by an 8-day program of adequate diet and exercise. The same number of age- and sex-matched control subjects were studied. During the first and eighth nights of the program, BP was obtained by ambulatory monitoring. After a 10-min rest, 3 BP and heart rate (HR) recordings were taken and the mean values were considered to represent their awake values. The monitor was programmed to cuff insufflation every 20 min from 10:00 p.m. to 7:00 a.m. The glycemic control of diabetics improved since glycemia (212.0+ 91.5 to 140.2+69.1 mg/dl, P<0.03), urine glucose (12.7+11.8 to 8.6+6.4 g/24h, P=0.08) and insulin dose (31.1+7.7 to 16.1+9.7 U/day, P<0.01) were reduced on the last day. The mean BP of control subjects markedly decreased during the sleeping hours of night 1 (92.3+6.4 to 78.1+5.0 mmHg, P<0.001) and night 8 (87.3+6.7 to 76.9+3.6 mmHg, P<0.001). Diabetic patients showed a slight decrease in mean BP during the first night. However, the fall in BP during the nocturnal period increased significantly on the eighth night. The average awake-sleep BP variation was significantly higher at the end of the study (4.2 vs 10.3 percent, P<0.05) and this ratio turned out to be similar to that found in the control group (10.3 vs 16.3 percent). HR variation also increased on the eighth night in the diabetics. Following the metabolic improvement obtained at the end of the period, the nocturnal BP variation of diabetics was close to the normal pattern. We suggest that amelioration of glycemic control may influence the awake-sleep BP and HR differences. This effect may be due at least in part to an attenuated insulin stimulation of sympthetic activity.

Different urinary albumin responses to submaximal exercise by normoalbumin-uric diabetic children and controls

It is not clear if exercise could be useful to identify diabetic patients at risk for the development of nephropathy. We evaluated the responses of blood pressure (BP) and urinary albumin (Alb) and retinol-binding protein (RBP) excretion to standardized sub-maximal exercise in 17 normoalbuminuric normotensive children with IDDM and 17 matched normal subjects. RBP was used as an index of tubular function. Standardization of exercise load was based on heart rate (HR) which was maintained at 70 per cent of the maximum calculated to age. A step exercise test lasted for 35 min; baseline BP and HR were taken at midtime and during cooling down. Pre- and postexercise urines were obtained for Alb, RBP and creatinine determinations. Both groups showed a significantly increased systolic BP at the midpoint but the percent variations were not different. HR responses did not differ and demonstrated the exercise effectiveness. Great variability in Alb excretion was observed within the normal range for both groups. The baseline Alb/creatinine ratio was not significantly different between normal and diabetic subjects, but became different following exercise (6.6 ñ 4.1 vs 17.7 ñ 18.7 mg/g, P<0.05). While this ratio decreased in the control group (14.8 ñ 11.1 to 6.6 ñ 4.1 mg/g, P<0.02), it increased (9.0 ñ 7.1 to 17.7 ñ 18.7 mg/g, P = 0.05) in diabetic patients. Percent variations in the two groups occurred in opposite directions and were significantly different. RBP/creatinine followed the same pattern within each group; normals showed a tendency to a decrease (0.058 ñ 0.064 to 0.030 ñ 0.039 mug/g, P = 0.05) and diabetic patients to an increase (0.116 ñ 0.125 to 0.247 ñ 0.247 mug/g, P = 0.06). We conclude that there was a variable proteinuric response to exercise among diabetic subjects with normal renal function as evaluated by albumin excretion. A subset of IDDM patients responded abnormally to the exercise stress, increasing albumin excretion to levels compatible with microalbuminuria. Whether this heterogeneity reflects individual risk for diabetic renal disease requires further investigation.

Effect of improved glycemic control on blood pressure and albuminuria of insulin-dependent diabetes without nephropathy

To assess the effect of glycemic control on blood pressure (BP) and albumin excretion rate (AER) in insulin-dependent diabetes, 35 patients (age 12.6 ñ 2.7 years) and 45 matched control subjects (11.9 ñ 1.8 years) were studied at an educational camp (Study I). They were evaluated at the beginning and at the end of a 9-day program of adequate diet and exercise twice daily, which induced statistically significant reductions in urinary glucose (18 ñ 21 to 5 ñ 7 g/12 h, P<0.01) and in insulin requirement (42 ñ 20 to 31 ñ 12 U/day, P<0.01) in the diabetic group. The mean BP and AER of the diabetic patients fell from 74 ñ 11 to 69ñ 11 mmHg,P<0.001, and from 4.9ñ 6.0 to 2.1 ñ 2.0 mug/min, P<0.01, and a correlation was found between AER and urinary glucose. In contrast, controls showed a lower reduction in BP and no change in AER. To evaluate the mechanisms involved in BP fall another group of 39 diabetics (age 12.7 ñ 2.1 years) was submitted to the same 9-day program and also to improved glycemic control (Study II). Changes in BP (79 ñ 11 to 76 ñ 11 mmHg, P<0.05) were slighter than in the previous study. Initial creatinine clearance was high and fell to the normal range at the end of the study (159 ñ 99 to 127 ñ 42 ml min(-1)(1.73 M2) (-1), P<0.05). Urinary aldosterone decreased from 5.3 ñ 3.9 to 3.4 ñ 2.4 mug/24 h (P<0.05), and fractional Na+ excretion tended to increase. Initial and final metanephrine values did not differ. Changes in mean BP did not correlate with changes in aldosterone, insulin requirement or urinary glucose. The decreases in hyperflltration and AER may have been due to the improved glycemic control induced by this educational program. Exercise may be responsible for BP reduction in diabetics and controls. BP changes particularly in diabetics could be attributed to the inhibition of the renin-angiotensin-aldosterone system and/or to decreased insulin requirement. The contribution of a negative Na+ balance consequent to decreased plasma insulin levels to the BP fall cannot be excluded.

Estudio comparativo de sensibilidad a la insulina en pacientes hipertensos con obesidad androide que utilizan amlodipina o propranolol / A comparative study of the effects of amlodipine and propranolol on insulin sensitivity in hypertensive patients with android obesity

Fueron estudiados 24 pacientes hipertensos con obesidad androide, sin intolerancia a la glucosa, con índice de masa corporal entre 25 y 35 kg/m2, con presión arterial diastólica superior a 95 mmHg e inferior a 115 mmHg, después de ocho semanas sin tratamiento farmacológico. Los pacientes fueron divididos en dos grupos de 12 pacientes y después de 4 semanas de administración de placebo recibieron amlodipina (5-10 mg/día) o propranolol (160-320 mg/día). Se realizó una prueba de sensibilidad a la insulina al término del período placebo y después de 20 semanas de tratamiento. Los niveles de presión se redujeron de manera semejante en los dos grupos. Antes del tratamiento con droga activa los dos grupos no diferían en cuanto al índice de sensibilidad a la insulina. El tratamiento con propranolol provocó una reducción significativa del índice de sensibilidad a la insulina (0,34 ñ 0,16 versus 0,23 ñ 0,09; p<0,05), mientras tal índice se mantuvo inalterado en el grupo tratado con amlodipina (0,33 ñ 0,29 versus 0,30 ñ 0,18; no significativo). El tratamiento de los pacientes hipertensos esenciales con propranolol resultó en un empeoramiento de la sensibilidad a la insulina, mientras la amlodipina no tuvo tal influencia deletérea

Radioimmunoassay of carboxyl and amino terminal fragments of parathyroid hormone for the evaluation of secondary hyperparathyroidism in chronic renal failure

1. Some parameters of calcium and phosphorus metabolism and the radioimmunoassay of plasma concentrations of both the carboxyl (COOH) (residues 53-84) and amino (NH2) terminal (residues 1-34) fragments of parathyroid hormone (PTH) were measured to evaluate secondary hyperparathyroidism in 68 patients with chronic renal falure (CRF), 34 of whon were on hemodialysis therapy. 2. The upper limits of the normal values for serum PTH-NH2 and PTH-COOH concentrations were 28 and 146 pmol/l, respectively. Patients with mild CRF (plasma creatinine (CRp) 1.2-2 mg/dl) hadh normal mean serum total calcium, low mean phosphorus, undetectable plasma levels of PTH-COOH concentration and normal fractional excretion of phosphorus (FEP). Patients with moderate CRF (CRp2.1-4 mg/dl) had normal mean serum concentrations of both total calcium and phosphorus, and elevated mean levels of both plasma PTH-COOH and PTH-NH2 associated with increased FEP. Patients with end-stage CRF (CRp > 4mg/dl) and those on hemodialysis had elevated mean serum phosphorus levels and decreased mean serum total calcium concentrations compared with those with mild and modetate CRF, and more pronounced, increases in both mean plasma PTH-COOH and PTH-NH2. 3. The logarithm of plasma PTH-NH2, but not PTH-COOH, concentration correlated positively with FEP and serum phosphorus concentration and negatively with total serum calcium concentration, while the logarithms of both PTH-NH2 and PTH-COOH levels correlated positively with CRp. 4. Calcium infusion (2 mg Kg-1 h-1 for 90 min) in eight patients with high plasma levels of PTH-NH2, and PTH-COOH resulted in a significant decrease of plasma PTH-NHL but not of plasma PTH-COOH concentration. 5. These data demonstrate increased plasma PTH levels in moderate renal failure and suggest that the assay of plasma PTH-NH2 rather than PTH-COLL is more appropriate for the evaluation of secondary hyperparathyroidism in chronic renal failure

Microalbuminuria, arterial blood pressure and retinopathy in insulin dependent diabetes

In order to evaluate the relationship between urinary albumin excretion, arterial blood pressure and diabetic retinopathy in insulin dependent diabetics we examined 55 patients without clinical proteinuria and whose disease had started before the age of 30. Each patient was asked to collect at least one overnight timed urine sample for albumin analysis by an ELISA method. Normoalbuminuria was defined as urinary albumin excretion (UAE) of < 20 mug/min (n = 32) and microalbuminuria as 21-200 mug/min (n = 23). Patients with microalbuminuria showed higher levels of blood pressure, serum creatinine and glicosylated haemoglobin as compared to normoalbuminuric patients. Significant correlation was observed between diastolic blood pressure and UAE (r = 0.52; p < O.001).Preproliferative and proliferative diabetic retinopathy was detected in 9 patients (l6.4 per cent). All of them had diabetes for more than 10 years, elevated UAE and diastolic blood pressure equal or higher than 85 mmHg. In our population of insulin dependent diabetics we found a high prevalence of microalbuminuria which is considered to be predictive of the latter development of diabetic nephropathy. Microalbuminuria is associated with elevated blood pressure and diabetic retinal lesions. We conclude that urinary albumin excretion should be monitored in patients with insulin dependent diabetes to detect those who should be considered at risk of developing nephropathy and retinopathy.

Tratamento do coma diabetico: experiencia em um hospital geral. / Treatment of diabetic coma: experience in a general hospital

O presente estudo mostrou que em nosso hospital o principal fator precipitante das descompensacoes diabeticas e a infeccao. Ressaltamos o baixo indice de mortalidade (1,4% nas cetoacidoses diabeticas e 8,8 no coma hiperosmolar nao cetotico) obtido com o esquema utilizado.Todos os nossos pacientes foram tratados a nivel de PS por uma equipe de residentes de Clinica Geral. Em nosso pais, onde centros endocrinologicos especializados se restringem as grandes concentracoes urbanas e de gran de importancia a divulgacao de esquemas terapeuticos de orientacao simples e que possam ser utilizados sem necessidade de grandes recursos materias, por clinicos gerais