Urinary kallikrein excretion in Bartter's syndrome.

Urinary excretion of kallikrein has been studied in a patient with hypokalemic alkalosis, hyperplasia of the renal juxtaglomerular apparatus and hyperreninemia, secondary aldosteronism and resistance to the pressor effect of angiotensin II (Bartter's syndrome). Urinary kallikrein was found exceedingly high in several determination, whereas it was low in patients with essential hypertension and high in patients with primary aldosteronism. Urinary kallikrein decreased after spironolactone therapy. The rise of kallikrein excretion (which is not related to plasma renin) in this case is probably caused by a direct action of the chronic excess of plasma aldosterone; it could not be accounted for as secondary to natriuresis.

Altered excretion of prostaglandin and thromboxane metabolites in pregnancy-induced hypertension.

The renal and systemic metabolites (the latter as 2,3-dinor derivatives) of prostacyclin and thromboxane A2 were measured, along with renal prostaglandin E2 and kallikrein, in the urine of 15 patients with pregnancy-induced hypertension, 15 normotensive pregnant women matched for both age and gestational age, and 15 normotensive nonpregnant control women. Urinary excretion of all prostaglandin and thromboxane metabolites studied proved significantly higher in normotensive pregnant women than in controls. Prostaglandin E2, 6-keto-prostaglandin F1 alpha, and 2,3-dinor-6-keto-prostaglandin F1 alpha were significantly lower in pregnancy-induced hypertensive women than in normotensive pregnant women, whereas thromboxane B2 and 2,3-dinor-thromboxane B2 showed no significant differences in the two groups. A significant negative correlation (r = -0.636, p less than 0.01) was found between urinary 2,3-dinor-6-keto-prostaglandin F1 alpha and mean blood pressure in the two groups of pregnant women taken as a whole. These data indicate that, in pregnancy-induced hypertension, there is an imbalance between vasodilator and vasoconstrictor factors, not only in the kidneys, but also at the systemic vascular level. This imbalance, which may in itself produce vasoconstriction, may also potentiate the hypertensive effect of catecholamines and angiotensin II.

Increased basal and thrombin-induced free calcium in platelets of essential hypertensive patients.

Intracellular free calcium, [Ca2+]i, was studied in platelets of essential hypertensive subjects and normotensive controls under basal conditions and after stimulation with epinephrine, norepinephrine, angiotensin II, ouabain, and thrombin, using the fluorescent calcium indicator quin 2. Basal [Ca2+]i was significantly higher in hypertensive subjects (n = 32) than in normotensive controls (n = 30; 167.4 +/- 5.0 vs 143.2 +/- 3.1 nmol/L; p less than 0.001). Epinephrine, norepinephrine, angiotensin II, and ouabain had no effect on platelet calcium, whereas thrombin induced a dose-dependent increase in [Ca2+]i in both the presence and absence of extracellular calcium. This [Ca2+]i increase in the presence of extracellular calcium, which depends mainly on calcium influx, was significantly higher (p less than 0.05) in platelets of hypertensive subjects at all thrombin concentrations (ranging from 0.025-0.1 U/ml), while the [Ca2+]i increase in the absence of extracellular calcium, which depends only on release from intracellular stores, was similar in hypertensive subjects and controls. These results suggest that, in essential hypertension, there is not only increased platelet resting [Ca2+]i but also an increase in agonist-mediated calcium influx, which appears to indicate a cell membrane abnormality in the platelets of subjects with essential hypertension.

Non-invasive detection of early endothelial dysfunction in hypercholesterolaemic subjects.

Hypercholesterolaemia is associated with accelerated atherogenesis. Before the evidence of morphological lesions or plaques, endothelial dysfunctions, such as impairment in endothelium-dependent vascular tone regulation, may occur. We studied 32 subjects, 16 with primary hypercholesterolaemia and 16 normocholesterolaemic controls. Flow-dependent vasodilation, an endothelium-dependent phenomenon, was evaluated by measuring femoral artery diameter and flow velocity in basal conditions and during distal post-ischemic hyperaemia, using a high resolution echo-Doppler. Arterial distensibility and compliance were evaluated for the common carotid and femoral arteries, using a pulsed echo-tracking system and measuring the absolute and relative stroke change in arterial diameter. In the hypercholesterolaemic group there was no flow-dependent arterial relaxation, indicated by the area under the curve of percentage diameter variation as a function of time. This parameter was inversely correlated with both total and LDL-cholesterol values in all population subjects. No difference was observed between the two groups in endothelium-independent vasodilation induced by glyceryl trinitrate administration or arterial wall distensibility and compliance, confirming the hypothesis of a functional defect.

Effect of losartan on heart rate and blood pressure variability during tilt test and trinitroglycerine vasodilation.

OBJECTIVE: To define the changes in variability of heart rate and of blood pressure during vasodilation in a group of hypertensive patients treated with an angiotensin II type I (AT1) receptor inhibitor. DESIGN: Losartan (50 mg/day at 0800 h) or placebo were administered for 3 weeks according to a single blind, crossover, randomized protocol, to 18 hypertensive patients (16 men and two women, mean age 42 + 3.6 years). Continuous ECG recording and beat-to-beat blood pressure monitoring were carried out with subjects in the supine position and during a head-up tilt test, as well as after sublingual administration of trinitroglycerine. The elaboration of ECG traces in the frequency domain, was carried out using an autoregressive method and measured using the autoregressive moving average technique. RESULTS: Orthostatic stimulus, both during treatment with losartan and with placebo, caused a significant decrease in the heart rate high frequency power; on the other hand, the low frequency power appeared unchanged after placebo and was significantly reduced with losartan. Five minutes after the administration of trinitroglycerine, the low frequency power with placebo showed a significant increase (817 -+ 221 versus 465 + 101 ms2, P < 0.03). No change was recorded in total power nor in low frequency or high frequency power during losartan therapy. The ratio of low frequency to high frequency powers showed a sympathetic prevalence during vasodilation only during placebo treatment, whereas a mainly unchanged balance was maintained during losartan treatment Blood pressure variability showed a sympathetic prevalence after upright and trinitroglycerine stimulation only in placebo-treated subjects. CONCLUSIONS: Our study demonstrated that vasodilation is not able to evoke an unbalancing of the autonomic modulation in hypertensive patients treated with an AT1 receptor inhibitor, but permits the maintenance of a significant vagal component, thus highlighting the favorable profile of this drug in the autonomic control of circulation.

Left ventricular diastolic function and responses to adrenergic stimuli in borderline arterial hypertension.

OBJECTIVE: To detect the existence of a possible relationship between arterial hypertension and adrenergic reactivity to pressure stimuli, and changes in left ventricular diastolic function (LVDF). PATIENTS: Fifty-nine young subjects with borderline arterial hypertension and ten sex- and age-matched controls were investigated. After three medical examinations, the subjects were divided into hypertensive and borderline groups on the basis of the blood pressure reading at visit 3. A complete echocardiographic study was performed in 25 of the 59 subjects. DESIGN: Blood pressure was measured in baseline conditions and during pressure stimuli (mental stress, handgrip and cold pressor tests). LVDF was evaluated primarily by means of filling velocities during diastolic phases taken from the left ventricular volume curve (obtained from a complete echocardiographic study). RESULTS: No significant changes in blood pressure responses were observed for the borderline or hypertensive groups during the adrenergic test. The echocardiographic indices of diastolic function were statistically different for the two groups when compared with the control group. The LVDF parameters correlated significantly with systolic blood pressure and diastolic blood pressure measured at the time of the echocardiogram, but not with blood pressure measured occasionally. CONCLUSIONS: Blood pressure increases similarly during adrenergic stimuli in both the hypertensive and borderline groups. The correlation between systolic blood pressure, diastolic blood pressure and LVDF parameters may indicate a very early onset of reduced compliance of the left ventricle, even in a preclinical phase of hypertension.

Fecal lipid chromatography--identification of an unusual fraction in relation to colon cancer.

The thin-layer chromatography of fecal lipids with revelation by phosphomolybdic reagent indicates the presence of an unusual fraction only in colon cancer patients. After isolation and identification, this fraction appears to be composed of coprostanol and its derivatives. The quantitative analysis of fecal neutral steroids in colon cancer patients compared to controls, patients with other digestive diseases and polypi shows a positive relationship between this fraction and colon cancer.

Intracellular free Ca2+ in platelets of essential hypertensive patients. Lack of correlation with clinical and laboratory data.

Platelet intracellular free Ca2+, [Ca2+]i, was found to be higher in 64 hypertensive patients than in 65 age- and sex-matched normotensive controls (142.7 +/- 3.8 nmol/l vs 126.6 +/- 2.4 nmol/l, M +/- SEM, respectively; P less than 0.001). No differences were observed in hypertensive patients in relation to age, duration of hypertension or severity of retinopathy, but a slight correlation was observed (r = 0.275, P less than 0.05) between platelet [Ca2+]i and systolic blood pressure. No correlations were found between platelet [Ca2+]i and plasma cholesterol, triglycerides, aldosterone or renin activity. These data appear to support the hypothesis that increased platelet [Ca2+]i in hypertensive patients is more likely to be related to a primary cellular abnormality than to activation by extrinsic humoral or vascular factors.

Reduction of the antihypertensive effect of captopril induced by prostaglandin synthetase inhibition.

The effects of prostaglandin synthetase inhibition by indomethacin on blood pressure and hormonal variations induced by captopril were studied in eight patients with essential hypertension and in six nonhypertensive subjects. Captopril antihypertensive effect and captopril-induced plasma renin increase were almost totally abolished by a short-term administration of indomethacin (50 mg t.i.d.). These results support the hypothesis that prostaglandins contribute to the antihypertensive effects of ACE inhibitors. It may be of clinical importance that anti-inflammatory drugs that inhibit PG-synthetase can also blunt the antihypertensive action of ACE inhibitors.

[Stability of alpha-tocopherol: pre-analytical conditions in its determination in blood samples]. / Stabilité de l'alpha-tocophérol: conditions préanalytiques à son dosage dans les prélèvements sanguins.

Incomplete and controversial data exist concerning vitamin E or alpha-tocopherol stability in biological samples. Recent clinical interest in the protective function of alpha-tocopherol provided another reason for the setting-up of a multicenter study by the Sociéte Française de Biologie Clinique. Our purpose was to examine the effects on alpha-tocopherol stability, firstly, of collection and transportation of blood samples, and, secondly, of the temperature (-20 degrees C and -80 degrees C) and period of storage of serum or plasma. alpha-tocopherol was determined in serum or plasma by isocratic liquid chromatography with UV detection at 292 nm. Our results established that alpha-tocopherol was extremely stable in blood, serum or plasma over 8 hours without special handling conditions (light, temperature). Pools of serum or plasma were stable for at least 3 months at -20 degrees C and -80 degrees C. They are suitable for use in the quality control of alpha-tocopherol. On the other hand, in some samples, we observed great variability in the rate of alpha-tocopherol degradation. However, there was lesser degradation when these plasma samples were stored at -80 degrees C instead of -20 degrees C. We therefore do not advise storing serum or plasma for more than 1 month at -20 degrees C for more than 3 months at -80 degrees C. This latter temperature is recommended in epidemiological studies.

[Updating of relative data on tocopherols in clinical biochemistry]. / Actualisation des données relatives aux tocophérols en biochimie clinique.

The working group on lipophilic vitamins of the FSBC has reviewed current knowledge in the field of tocopherols and tried to summarize the most important and recent aspects that may be useful to clinical practitioners. The molecular structure of tocopherols and tocotrienols, their biogenesis, their analysis in foods, their metabolism in humans, their measurement in biological fluids, and the organism's needs and dietary requirements are reviewed. Their main functions as antioxidants and free radical scavengers are described at the molecular, ultra-structural, cellular and organ levels. The interest of these vitamins in three pathologies in which oxidative-stress has been implicated (atherosclerosis, cancer, kidney failure) is discussed.

Faecal lipid chromatography. I. Quantitative determination with chromarods.

A new and original method is proposed for the qualitative and quantitative analysis of faecal lipids by thin-layer chromatography and detection through the flame ionization detector of an analyser (the Iatroscan TH 10). This method enables the rapid quantification of the different faecal lipid classes, including cholesterol, with great accuracy and reproducibility. In-series operations are possible with easy manipulation.

Measuring water content of feces by the Karl Fischer method.

We describe a technique for measuring the water content of stools by the Karl Fischer method. The analysis is based on removal of water into a mixture of methanol/chloroform (1/2), after dispersion of the stool by sonication in presence of solvent. An aliquot of the solution thus obtained is placed in themeasuring cell of a Karl Fischer apparatus and then analyzed in the classic way. We further describe the advantages of this method (odorless, precise, reproducible) in contrast to other current methods. In addition the same organic solution can also be used in determining the lipid content of stools.