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Pancera P, Sansone S, Secchi S, Covi G, Lechi A (University of Verona, Verona, Italy). The effects of thromboxane A2 inhibition (Picotamide) and angiotensin II receptor blockade (Losartan) in primary Raynaud's phenomenon. J Intern Med 1997; 242: 373–6. Objectives To assess the role of thromboxane A2 and of angiotensin II in patients with primary Raynaud's phenomenon. Design After an eight-day run-in period, the patients were enrolled in a single-blind, cross-over, study. Setting Patients were examined at the Ambulatory for Microcirculatory Diseases of the Clinic of Internal Medicine, University Hospital, Verona. Subjects Fifteen subjects affected by primary Raynaud's phenomenon were included. Main outcome measures A piezoelectric plethysmography to evaluate the distensibility of the digital arteries as the ratio between peak time (PT) and total time (TT), and an oscillometric blood pressure recorder were used after the run-in period, and after a two-week course of picotamide (300 mg b.i.d., i.e. two times daily) or losartan (12.5 mg once daily) with an interval of a week of placebo between the active treatments. The tests were performed after every treatment in basal condition and during mental stress. The patients reported in a diary the number and the severity (from 0 to 4 +) of the vasospastic crises. Results The change in TP/TT ratio appeared statistically significant only after losartan treatment, both in basal condition and during mathematical stress. Both pharmacological treatments, with respect to placebo, showed an improvement of the scores, derived from the number and severity of vasospastic attacks, but only the therapy with losartan determined a statistically significant improvement. Conclusions The inhibition of the type 1 receptor for angiotensin II seems highly effective in the reduction of the vasospastic crises in the subjects with primary Raynaud's phenomenon. According to our experience, losartan could be used more extensively in the treatment of these patients besides arterial hypertension.

Eighteen subjects distressed by memories of a specific traumatic event were randomly assigned to a single session of one of three conditions: Eye Movement Desensitization and Reprocessing (EMDR), a Time Interval Condition (TIC), or Tapping Alternate Phalanges (TAP). All subjects treated in the EMDR group showed desensitization as monitored by SUDs, which correlated with the physiological data and cessation of pronounced symptomatology. Only one subject in a control group showed desensitization. Compared to TIC and TAP, autonomic measures showed distinct changes during EMDR: (1) respiration synchronized with the rhythm of the eye movements in a shallow, regular pattern; (2) heart rate slowed significantly overall; (3) systolic blood pressure increased during early sets, invariably declined during abreactions, and decreased overall; (4) finger tip skin temperature consistently increased; and (5) the galvanic skin response consistently decreased in a clear “relaxation response.” This relaxing effect of the eye movements suggests that at least one of the mechanisms operating during EMDR is desensitization by reciprocal inhibition, by pairing emotional distress with an unlearned or “compelled” relaxation response.

Resume La prise en charge et le suivi des patients hospitalises pour infarctus du myocarde (IDM), ou menace d'IDM, varie selon les sites, en fonction notamment du plateau technique dont disposent les cardiologues. Le but de ce travail est, a partir d'une relfexion menee conjointement par des biologistes et des cardiologues, de verifier la qualite des informations foumies par des examens biologiques et des cardiologues, de verifier la qualite des informations fournies par des examens biologiques habituellement prescrits et de reconstituer une serotheque significative pour l'etude de nouveaux « candidatsmarqueurs de l'IDM utilisables en urgence. Quatre objectifs precis sont plus particulierement definis : verifier sur le plan analytique la concordance de differents systemes analytiques ; verifier l'interet de la myoglobine serique dans le diagnostic de I'IDM particulierement lorsque la clinique et l'electrocardiogramme sont peu parlants ; verifier son interet dans le suivi a court terme des patients thrombolyses ; enfin, comparer les valeurs informatives de la myoglobine et de la CKMB dans ces deux indications, ceci dans le but de definir une strategie de prise en charge des patients. Un protocole commun est mis en place sur cinq sites hospitaliers. Le critere d'inclusion des patients dans l'etude est l'admission dans un service de cardiologie pour douleur thoracique. Les prelevements sanguins sont effectues a l'arrivee du patient dans le service de cardiologie et lors de la thrombolyse. La myoglobine est dosee par immunofluorometrie (Stratus-Baxter a Dourdan et Saint-Germain-en-Laye) ou par turbidimetrie (Turbitimer-Behring a Calais, Douai et Lens), la CKMB ponderale est mesuree dans les differents sites sur Stratus ou IMX quant a l'activite enzymatique de la CK totale, elle est mesuree sur les automates de routine installes dans chaque site. Pour ces deux parametres, myoglobine et CKMB, la repetabilite (

Objective: The aim of this prospective study was to establish whether or not there is any relationship between activation of the prostaglandin system and changes in systemic and uteroplacental hemodynamics in pregnancy.Methods: Urinary excretion of prostaglandin E2 (PGE2) and the main metabolites of prostacyclin (PGI2) and thromboxane A2 (TXA2) was determined, and indices of the vascular resistance of the uteroplacental bed were measured in 10 normotensive women studied in each trimester of pregnancy and in 15 women with pregnancy-induced hypertension in the third trimester. None of these subjects presented renal insufficiency or coagulation disorders, and all were monitored up to delivery to assess the outcome of pregnancy. Urinary excretion of prostanoids was measured by radioimmunoassay after purification of samples with high-pressure liquid chromatography. Blood pressure was measured and vascular resistance indices were calculated, using ultrasonography to measure the amplitude of systolic and diastol...

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.

As suggested by findings of abnormal responses to posture in patients with normal-tension glaucoma (NTG), cardiovascular autoregulation may also be defective in primary open-angle glaucoma (POAG).Both 24-hour ambulatory blood pressure monitoring and the head-up tilt test were performed in 17 subjects with NTG and in 13 subjects with high-tension POAG (ht-POAG). These groups were compared with 17 age-matched healthy individuals. Subjects undergoing cardiovascular therapy were excluded.No significant differences in diurnal and nocturnal blood pressure and heart rate were found between the groups. A significant reduction in diurnal heart rate variability was found in NTG (12.1 +/- 2.8 bpm) compared with the ht-POAG (15.0 +/- 2.4 bpm, P0.01) and control groups (15.8 +/- 3.0 bpm, P = 0.01]). Nocturnal diastolic blood pressure variability was also reduced in NTG (6.9 +/- 2.2 mm Hg) compared with controls (8.6 +/- 2.3 mm Hg, P0.05]) as was heart rate variability (6.3 +/- 1.4 vs 8.3 +/- 2.6 in ht-POAG, P0.05), suggesting blunted blood pressure and heart rate modulation in NTG subjects. Spectral analysis of short-term heart rate variability showed a significant reduction of total power in the supine position (1064 +/- 600 in NTG vs 1688 +/- 889 ms2 in controls, P0.05]). This was not accompanied either by a physiological reduction in total power or in a high-frequency component during the passive orthostatic stimulus. These differences tend to become more prominent in the clinically more severe forms of NTG (as identified by scores based on the extent of optic disk excavation, visual field damage, and progression of disease). This would suggest a correlation between the extent of autonomic disorder and severity of glaucoma. The alpha index (root-square of low-frequency heart rate to low-frequency blood pressure ratio) was lower in the supine position in NTG subjects (8.1 +/- 3.1 vs 10.6 +/- 3.3 ms/mm Hg in controls, P0.05), confirming the reduced baroreflex sensitivity.The results confirm the hypothesis that dysfunction of autonomic control of the cardiovascular response may be a contributing pathogenetic factor in NTG, inducing a chronic ischemia of the optic nerve.

OBJECTIVE: To ascertain in obesity the role of body fat distribution (the strongest predictor of morbility and mortality in obese subjects) in determining the degree of endothelial dysfunction, an early marker of atherosclerotic disease. SUBJECTS: 18 premenopausal women with uncomplicated obesity excluding other cardiovascular risk factors and 12 age-matched slim healthy women. MEASUREMENTS: Endothelium-dependent vasodilation, studied as diameter variation in response to an increase in shear-stress, was evaluated in the right common femoral artery of obese and slim subjects by a non invasive approach and compared to glyceril-trinitrate vasodilation. To characterize better the vascular functional and/or structural properties, we studied the arterial wall distensibility by an echo-tracking system. Adipose tissue regional distribution was determined by computerised axial tomography. RESULTS: The endothelium-dependent vasodilation was significantly impaired in obese subjects (P

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.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.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, P0.03). 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.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.

We studied the changes in left ventricular (LV) diastolic function induced by angiotensin-converting enzyme (ACE) inhibition at rest and during adrenergic stimulation and their relation to blood pressure (BP) variations to determine whether reductions in the renin-angiotensin system may improve diastolic function irrespective of BP reduction. Echocardiographic indices of systolic and diastolic function, plasma catecholamines as estimated by high-pressure liquid chromatography, and BP variations (Dynamap) were determined at rest and during the cold pressor test (CPT) before and 6 hours and 20 days after ACE inhibition (lisinopril), 20 mg/day by mouth in 10 subjects with uncomplicated essential hypertension. Blood Pressure was significantly reduced after both 6 hours and 20 days of therapy. The cold pressor test induced similar increases in BP in both basal conditions and after acute and chronic treatment. Catecholamine levels were unchanged by the therapy. Systolic function, evaluated by fractional shortening, ejection fraction, and systolic dV/dt, was normal and unchanged during CPT and after treatment. Diastolic function, assessed by volume curve analysis, showed a reduced percentage contribution of rapid filling to total diastolic filling, an increase in the contribution of the atrial systole, and an increase in the isovolumetric relaxation time. During CPT these parameters deteriorated further in response to increased afterload. Lisinopril therapy induced significant increases in end-diastolic volume (p0.005) with a progressive increase in the rapid filling dV/dt (p0.005 at rest; p0.001 during CPT) and a reduction in isovolumetric relaxation (p0.0001 at rest and p0.01 during CPT). The correlation between systolic BP (afterload) and the rapid filling dV/dt, both at rest and during CPT, was modified by treatment with the ACE inhibitor, with significantly higher rapid filling dV/dt values, and with the pressure loads equal (reduction of the slope and rightward shift of the correlation line). The improvement in diastolic function achieved by ACE inhibition at rest and during CPT appears unrelated to plasma catecholamines and only partly ascribable to the reduced pressure load. The tissue angiotensin II reduction might by itself improve the myocardial response to the pressure load and adrenergic stimulation.

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.

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.

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.

Passive tobacco smoking is responsible for increased respiratory morbidity in young children. This point is not always understood by parents and the use of a sensitive marker for nicotine exposure may help them to smoke less.Urinary cotinine concentration was measured in 72 children, aged from 1 to 5 years, that had been admitted to our unit during October and November 1991 for various causes. The results were correlated with the smoking habits of their parents. Urine samples were obtained during the first hours after admission and the cotinine concentration was measured by HPLC. Concentrations5 micrograms per liter were considered to be positive.A total of 67 urine samples were analysed: 43 (64.2%) were positive with cotinine concentrations of 5 to 77 micrograms/l (mean: 19.7). Both parents of 21 children were smokers; the fathers of 18 children and the mothers of 11 children, alone, smoked. There was therefore at least one smoker in the environment of 50 children. There was a highly positive correlation between parental smoking and urinary cotinine (p0.0001). For the infants with only one parent who was a smoker, their urinary cotinine was higher when the smoker was the mother rather than the father.An urinary cotinine of6 micrograms per liter is a precise, sensitive, test for passive smoking in young children. This test is well accepted by families and its result may persuade parents to stop or moderate their use of tobacco. This test also could be used, as part of a pulmonary check-up, as a public health indicator.

The effect of vaginal administration of a PgE 1 analogue to terminate missed abortion and fetal death in utero was evaluated in 62 women with gestation ranging from the 13th to the 37th week. Abortion occurred in 85.4% of women with missed abortion and in 86% of women with fetal death. In both groups, the mean induction time was less than 12 h. The incidence of side effects, primarily gastro-intestinal symptoms, was infrequent.

The effects of nifedipine on blood pressure (BP), left ventricular hypertrophy, and diastolic function were evaluated in 14 patients with essential hypertension (EH). All males with a mean age of 44 +/- 6 years (range 35-58 years), and in ten normotensive subjects (control group) aged 32-42 years (mean age 36 +/- 4). A complete echocardiogram (ECHO) was performed in basal conditions after 1 and 6 months of therapy with nifedipine (20-40 mg/day). Left ventricular echocardiograms (LV ECHO, M-mode, two-dimensional guided) were plotted with a simultaneous ECG tracing by means of a computerized system that allows evaluation of the following parameters: LV end-diastolic and systolic diameters (EDD, ESD); variations in LV diameter and volume during the entire cardiac cycle, and the velocities of such variations; end-diastolic thicknesses of the interventricular septum and posterior wall (ST, PWT); LV mass, mass/volume (M/V) index, end-diastolic diameter/thickness (D/Th) index, and LV ejection fraction (EF). Left ventricular volume curves were obtained and the contributions of rapid filling (RF) and atrial systole (AS) to EDV were evaluated. Filling velocities during RF (vRF) and AS (vAS) were estimated, as well as the isovolumic relaxation period (IR). No significant changes were observed in the heart rate. After 1 month of therapy, systolic and diastolic BP were significantly decreased (p less than 0.05). ST and PWT were reduced, with a simultaneous increase in EDD and EDV (p less than 0.01). LV mass was slightly reduced, as was the M/V index. The D/Th index was increased (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Urinary excretion of calcium, sodium, creatinine, proteins and renal prostaglandins (PGE2, 6kPGF1α) and serum levels of calcium, sodium, creatinine and albumin were determined in 10 normotensive pregnant women throughout pregnancy and in 30 normotensive pregnant women (NTP) and 30 women with pregnancy-induced hypertension or preeclampsia (HTP) and intact kidney function in the third trimester in comparison with 13 nonpregnant control subjects (C).Urinary excretion of calcium was found to be significantly reduced in the HTP group and was correlated with PGE2 excretion (p < 0.01). A weak correlation was detectable in the NTP group, which, however, as in the HTP and C groups, showed a close correlation between urinary calcium and sodium values (p < 0.05). In the NTP group, there was a significant increase in calcium excretion, which might reasonably be regarded as related to increased renal PG activity.

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.

To compare the clinical and metabolic effects of a new diuretic uricosuric agent, tienilic acid, with those of hydrochlorothiazide, a multicentre double-blind trial was performed in 56 hypertensive patients. Twenty — eight patients were randomly assigned to take tienilic acid and 28 to take hydrochlorothiazide. The diuretic and anti-hypertensive actions of the two compounds were similar. No significant differences were observed between tienilic acid and hydrochlorothiazide in their effects on urinary and serum electrolytes, hepatic and renal function tests, and fasting lipids. The patients who received tienilic acid showed a significant fall in serum uric acid, mediated by the uricosuric effect. The availability of an agent combining diuretic, anti-hypertensive and hypouricemic effects offers promise in the treatment of arterial hypertension.

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.

1. Outward bumetanide-sensitive Na+-K+ co-transport was studied in the erythrocytes of 51 subjects, 24 normotensive subjects and 27 hypertensive patients, matched for sex and age. 2. Three kinetic parameters of this cation transport system were considered: velocity of efflux at saturating internal sodium (Nai) concentrations (Vmax.), apparent affinity for sodium (K50%) and index of co-operativity among Nai sites (Hill's n). 3. We correlated these values with clinical and laboratory data determined routinely in hypertension. 4. There were no significant differences between normotensive and hypertensive subjects for the values considered and we did not find any significant correlations between co-transport and clinical data.

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.

The effects of two antihypertensive agents, nifedipine (N) and captopril (C), on left ventricular (LV) mass and volume were studied in 16 patients with essential hypertension (8 treated with N and 8 with C for 6 months) by means of a complete M-mode echocardiogram monitored by two-dimensional echocardiography. Both N and C induced a significant reduction in end-diastolic, but not systolic, posterior wall and septum thickness and an increase in end-diastolic volume, but not in end-systolic volume. A significant increase in the contribution of rapid filling together with a simultaneous reduction in the contribution of atrial systole to end diastolic volume were also observed. The reduction in LV wall thickness and mass after both C and N might be attributed to an improvement in diastolic function and to a reduction in wall tension, rather than to an effective regression of LV hypertrophy.

1. Tienilic acid and hydrochlorothiazide were evaluated in a double-blind trial in order to investigate their antihypertensive and metabolic effects. 2. After 5 weeks, the decreases in blood pressure and the changes in plasma or serum electrolytes, urea, creatinine, glucose, cholesterol and triglycerides, and in creatinine clearance, did not differ in the two groups of patients. 3. In patients taking tienilic acid a significant decrease in serum uric acid and an increase in urate clearance was observed, whereas in patients receiving hydrochlorothiazide a slight increase in serum uric acid, with no modification of urate clearance, occurred. 4. The diuretic and antihypertensive actions of tienilic acid and hydrochlorothiazide are very similar. The uricosuric/hypouricaemic effect of tienilic acid could assume clinical relevance in long-term therapy of hypertensive patients.

Urinary and kidney kallikrein were studied in rats with renal clip hypertension. The effect of protease inhibitors on urinary and kidney BAEE esterase activity was similar. Both hypertensive and not hypertensive operated rats excrete significantly less kallikrein than controls; in the ischaemic kidney kallikrein is diminished whereas is not increased in contralateral. Kallikrein is therefore related to renal functional mass but does not seem responsible for a natriuretic effect.

Angiotensin-converting enzyme (ACE) inhibitors reduce blood pressure (BP) by two possible mechanisms: reducing the formation of angiotensin II and aldosterone, and increasing the production of kinins (angiotensin-converting enzyme is also a kininase II) (Figure 1). This leads to a decreased vasoconstriction of the kinin and to a potentiation vasodepressor system with vasodilatory and antihypertensive effectsl. A rise in kinin levels stimulates an increased synthesis of vasodepressor prostaglandins (PGs), especially prostacyclin (PGI2)2. Moreover, some authors have shown an increase in PG production after captopril administration3–5. Therefore the prostaglandin system could be involved in the mechanism of action of ACE inhibitors and prostaglandin synthetase inhibitors could reduce their antihypertensive activity. In man a reduction of the antihypertensive activity of ACE inhibitors was observed when non-steroidal anti-inflammatory drugs (NSAIDs) were administered6,7.

Recent reports have described high levels of one or more substances which cross-react with digoxin antibodies in the serum of women with pre-eclampsia. We measured plasma ouabain-like activity and intra-erythrocyte sodium and potassium concentrations, in addition to performing routine hypertensive laboratory tests, in 13 normotensive non-pregnant subjects, 15 normotensive pregnant women and 16 pre-eclamptic women (gestational age: 33–36 weeks). Plasma ouabain-like activity, measured as plasma-induced variations in ouabain binding to human erythrocytes, proved significantly higher in both groups of pregnant subjects as compared to normotensive non-pregnant women, and a significant difference was also found between pre-eclamptic and normotensive pregnant women, the former exhibiting higher plasma ouabain-like activity. No differences in intracellular sodium and potassium levels were detected among the three groups studied. Though there is reason to believe that the high plasma levels found both in normal and hypertensive pregnancy may depend on placental production, we are not in a position to define with any degree of certainty what the mechanism or mechanisms are that regulate ouabain-like factor production.

The role of prostaglandin (PG) system in preeclampsia (pre-E) was investigated. Urinary excretion of PGE2,6-keto PGF1 alpha,2,3 dinor 6-keto PGF1 alpha, TxB2 and 2,3-dinor-TxB2 and kallikrein were determined in 10 normotensive pregnant women and 14 with pre-E. 6-keto PGF1 alpha and 2,3-dinor 6-keto PGF1 alpha (the main renal and extrarenal metabolites of vasodilator PGI2) and PGE2 excretion was lower in pre-E. TxB2 metabolites in urine were similar in the two groups of women. Our data are consistent with the hypothesis of an imbalance between vasodilator and vasoconstrictor PGs in pre-E.

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.

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.

1. The 24 h urinary excretion of kallikrein has been studied in 40 normotensive control subjects and in 74 age-matched patients with essential hypertension under similar conditions. By use of the renin-sodium index, hypertensive patients were divided into two subgroups: low-renin hypertension and normal-renin hypertension patients. Urinary kallikrein determinations were also obtained from six hypertensive patients with primary aldosteronism. 2. Urinary kallikrein was significantly lower both in patients with normal-renin and low-renin essential hypertension. Urinary kallikrein excretion was very high in the patients with primary aldosteronism. 3. In nine hypertensive patients β-adrenoreceptor-blocking therapy caused a significant decrease of plasma renin activity, but had no significant effect on urinary kallikrein excretion. 4. The results support the concept that low urinary kallikrein is likely to be a marker of essential hypertension. Under certain conditions its excretion is positively related to mineralocorticoid hormone concentrations but it is not primarily related to the renin-angiotensin system.

The exogenous administration of pharmacological doses of mineralocorticoids causes a transient sodium retention which is followed after a few days by a return to a new sodium balance. This latter phenomenon, known as escape from the sodium-retaining effects of mineralocorticoids, is characterized by an increased urinary volume and sodium excretion. At the same time increased renal blood flow, glomerular filtration rate and reduced renal vascular resistance are observedl. Besides the haemodynamic factors, prostaglandins (PGs) and kallikreinkinin system have been suggested as being responsible, at least partly, for the escape phenomenon.

2-Hydroxy-(1-hydroxy-[(1-methyl-3-phenylpropyl)amino]-2-ethyl)-5-benzamide (labetalol), a new alpha- and beta-adrenergic blocking agent, was employed in 21 patients with severe hypertension by slow (6 patients) and rapid (15 patients) i.v. infusion. A marked and significant fall of blood pressure was observed in both groups, though more gradual in patients treated by slow infusion. A rapid blood pressure fall with cardiac output decrease was observed by passing from supine to standing position in the first hours after infusion. Therefore, it is advisable to keep a supine position for a few hours. Plasma renin activity decreased after labetalol infusion, but basal plasma renin levels were not related to hypotensive effect of labetalol. In slow infusion patients, plasma noradrenaline levels increased and no changes of plasma adrenaline levels were observed during infusion. The most likely explanation of these variations is an increase of sympathetic activity secondary to hypotension, caused by labetalol, whereas a technical interference seems to be excluded. The simultaneous blockade of alpha- and beta-receptors can inhibit, in this case, the pressor effects of the sympathetic reflex.

The effects of a single oral dose (100 mg) of the angiotensin-converting enzyme (ACE) inhibitor, captopril (SQ 14,224), on blood pressure (BP), plasma renin activity (PRA), plasma aldosterone (PA), and serum ACE were investigated in 18 patients with essential hypertension (EH) and in 4 with renovascular hypertension (RVH). in most patients, SQ 14,225 caused a significant reduction of BP during the subsequent 6 h, particularly in RVH patients. A significant correlation between basal PRA levels and BP reduction was observed only by considering all the patients together. After ACE blockade, a significant increase of PRA was observed in RVH and in normal-renin EH patients, but not in EH patients with lower PRA. Maximal serum ACE inhibition (over 50%) occurred after 2 h but diminished after 4 h and 6 h, whereas the BP decrease persisted for 6 h. After 3-day treatment with indomethacin (six patients) captopril's antihypertensive action was blunted, despite a reduction of baseline PRA levels and of captopril-induced PRA elevation. The antihypertensive effects of SQ 14,225 in low-renin EH patients, the lack of effect of ACE blockade on renin secretion in these patients, and the reduction of the antihypertensive effects of SQ 14,225 after indomethacin refute the interpretation of purely angiotensin-related antihypertensive mechanism.

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.

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.