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Biomedical subjects

R Fagard

Publications and source records attributed to R Fagard.

At least 253 records · Page 14Linked to original sources
PubMed1990

Effects of nitrendipine and atenolol on blood pressure and intracellular sodium in hypertensive blacks.

Thirty-five hypertensive black patients were randomized in a double-blind fashion to receive either atenolol 100 mg per day (n = 17) or nitrendipine 20 mg daily (n = 18) for six weeks. Atenolol and nitrendipine significantly reduced blood pressure (P less than 0.05 or less). However, the magnitude of the decrease in supine systolic blood pressure (SBP) and diastolic blood pressure (DBP), and in standing diastolic pressure was more pronounced (P less than 0.05 or less) in the nitrendipine than in the atenolol group. Neither of the drugs significantly affected the erythrocyte sodium and potassium concentrations or the ouabain-sensitive efflux of sodium. In multiple regression analysis the changes in supine SBP and DBP with nitrendipine were independently and negatively correlated with the patients' age and initial blood pressure, and positively with the change in supine pulse rate; the change in supine SBP was also negatively correlated with initial erythrocyte sodium concentration. Our results suggest that nitrendipine is more efficient than atenolol in hypertensive blacks and that besides older age and higher pre-treatment. BP levels, a higher intracellular sodium concentration could predict a greater response to nitrendipine.

Atenolol↗
PubMed1990

Evidence for a curvilinear relation between blood pressure and urinary sodium in men.

With the use of a linear model, the relation between urinary sodium and blood pressure has been reported to be positive, non-significant, or negative. The hypothesis that this relationship is more complex than linear was investigated in two different study populations, which were independently recruited and examined by different observers. In 1,071 men randomly selected from the general population and in an unrelated sample of 1,209 military men, systolic and diastolic blood pressure were correlated with urinary sodium following a model, which included both the linear and quadratic terms of urinary sodium. In both groups of men, these second order models, adjusted for age and body mass index, provided a better fit (P less than 0.05) than the relationships with only the linear term of urinary sodium. The quadratic models explained from 0.35 to 1.10% of the blood pressure variance. Third order models, which in addition included the cubic term of urinary sodium, did not further improve the correlations between systolic and diastolic blood pressure and urinary sodium in men. In 1,010 women drawn from the general population and in 499 military women, neither the first nor the second order correlations between systolic and diastolic blood pressure and urinary sodium were statistically significant. In conclusion, the present results, reproducible in two different study populations, suggest that a second order model is more appropriate than a simple linear correlation to describe the weak relationship between blood pressure and urinary sodium in men. However, recommendations for the prevention of hypertension must not be changed, until the present findings are confirmed by intervention studies.

Adolescent↗
PubMed1990

Inhibition of human erythrocyte and leukocyte Na+, K(+)-pump activity by lysophosphatidylcholines.

Synthetic lysophosphatidylcholines (LPCs) were examined for their effects on erythrocyte and leukocyte Na+,K(+)-pump activity, on erythrocyte Na+,K(+)-cotransport activity and on the passive permeability of the red blood cell membrane. Erythrocyte and leukocyte Na+,K(+)-pump activity was estimated by ouabain-sensitive 86Rb-uptake and erythrocyte Na+,K(+)-cotransport activity by bumetanide-sensitive 86Rb-uptake. Bumetanide, ouabain-resistant 86Rb-uptake was considered as a measure of the passive permeability of the red blood cell membrane. LPCs containing long chain fatty acids such as myristoyl, palmitoyl, lauroyl, stearoyl and oleoyl inhibited erythrocyte and leukocyte Na+,K(+)-pump activity and erythrocyte Na+,K(+)-cotransport activity, while they stimulated the passive membrane permeability of the red blood cells. LPCs containing lauroyl, the shortest fatty acid in this group, had the lowest inhibitory activity, while LPCs with intermediate chain length fatty acids such as caproyl and decanoyl had no effect. The order of inhibitory action of these LPCs on erythrocyte and leukocyte Na+,K(+)-pump activity was: palmitoyl greater than stearoyl greater than myristoyl greater than oleoyl greater than lauroyl.

Adult↗
PubMed1989

Urapidil-induced hemodynamic changes in humans.

In hypertensive patients as well as in normal subjects urapidil has a hypotensive action. This is mainly mediated by a peripheral alpha 1-adrenoceptor blockade with a decrease in systemic vascular resistance; in addition, during acute animal experiments a centrally mediated hypotensive action was demonstrated, possibly by 5-hydroxytryptamine1A (5-HT1A)-receptor stimulation. Studies in humans showed an increase in cardiac output, which was not always significant; it did result either from an increased heart rate or an increased stroke volume. Acute changes in pulmonary hemodynamics after administration of urapidil were most pronounced in patients with pulmonary hypertension: pulmonary artery pressure and pulmonary vascular resistance decreased significantly and pulmonary capillary wedge pressure decreased nonsignificantly. A small reduction in pulmonary artery pressure and capillary wedge pressure were seen in patients with congestive heart failure and in patients in whom acute blood pressure elevation developed after coronary bypass surgery. In patients with essential hypertension forearm, renal and splanchnic flow were shown to increase and vascular resistance to decrease significantly after acute intravenous doses of urapidil. The hemodynamic changes during chronic therapy are largely unknown, except for systemic vascular resistance which remains decreased.

Acute Disease↗
PubMed1989

Phosphorylation of p56lck by external ATP in intact cells.

Recent studies have suggested a role for extracellular ATP. In this report we show that extracellular labelled ATP crosses the plasma membrane of intact lymphoma cells and peripheral blood lymphocytes and phosphorylates p56lck a tyrosine protein kinase specific of lymphoid cells. Two other phosphoproteins of 92Kd and 35Kd become detectable on alkali treated gels. Phosphorylation occurs within minutes following addition of ATP. ATP, GTP, ADP and an ATP analog prevent phosphorylation but not AMP nor Pi; trypsinization of cells abolishes labelling. The possible involvement of P2 purinergic receptors is discussed.

Adenosine Triphosphate↗
PubMed1989

Relation between mortality and treated blood pressure in elderly patients with hypertension: report of the European Working Party on High Blood Pressure in the Elderly.

OBJECTIVE: To investigate the relation between mortality and treated systolic and diastolic blood pressures. DESIGN: Randomised double blind placebo controlled trial. Mortality in the two treatment groups was examined in thirds of treated systolic and diastolic blood pressures. PATIENTS: 339 And 352 patients allocated to placebo and active treatment, respectively. The groups were similar at randomisation in sex ratio (70% women), mean age (71.5 years), blood pressure (182/101 mm Hg), and proportion of patients with cardiovascular complications (35%). MEASUREMENTS AND MAIN RESULTS: In the placebo group total mortality rose with increasing systolic pressure whereas it had a U shaped relation with diastolic pressure, the total lowest mortality being in patients in the middle third of the distribution of diastolic pressure. In the group given active treatment total mortality showed a U shaped relation with systolic pressure and an inverse association with treated diastolic pressure. In both groups cardiovascular and non-cardiovascular mortality followed the same trends as total mortality. The increased mortality in the lowest thirds of pressure was not associated with an increased proportion of patients with cardiovascular complications at randomisation or with a fall in diastolic pressure exceeding the median fall in pressure in each group. In contrast, patients in the lowest thirds of pressure showed greater decreases in body weight and haemoglobin concentration than those in the middle and upper thirds of pressure. CONCLUSIONS: In patients taking active treatment total mortality was increased in the lowest thirds of treated systolic and diastolic blood pressures. This increased mortality is not necessarily explained by an exaggerated reduction in pressure induced by drugs as for diastolic pressure a U shaped relation also existed during treatment with placebo. In addition, patients in the lowest thirds of systolic and diastolic pressures were characterised by decreases in body weight and haemoglobin concentration, and the patients in the lowest thirds of diastolic pressure taking active treatment also by an increased non-cardiovascular mortality, suggesting some deterioration of general health.

Aged↗
PubMed1989

High pp60c-src level in human platelet dense bodies.

Phosphoproteins phosphorylated in vivo were examined in resting and thrombin-activated human blood platelets. Thrombin-stimulation resulted in an overall increase in labeled proteins containing phosphotyrosine. The most prominent was a protein of 60 Kd. By electroblotting, the 60 Kd protein was identified as the pp60c-src, the normal cellular homolog of the transforming protein of Rous sarcoma virus. We have examined the intracellular distribution of the pp60c-src within platelets. Use of immunoprecipitation and electrotransfer to study isolated membranes, alpha-granules, lysosomes, and dense granules (also termed dense bodies) revealed that pp60c-src was highly enriched in dense bodies. In view of the prominent role of these granules in platelet function, We postulate that protein phosphorylation by activated pp60c-src is involved in early steps of platelet activation.

Blood Platelets↗
PubMed1989

Effect of endurance training on blood pressure at rest, during exercise and during 24 hours in sedentary men.

The effect of 4 months of physical training on resting, exercise and 24-hour blood pressure (BP) was studied using a randomized crossover design in 26 healthy, sedentary men, with an average age of 39 +/- 10 (standard deviation) years. Peak oxygen uptake increased by 14% (p less than 0.001) and the physical working capacity at a heart rate of 130 beats/min by 25% (p less than 0.001). The heart rate was reduced by 7 beats/min at night (p less than 0.01) and by 6 beats/min during the day (p less than 0.001). Training-induced changes of BP varied according to measuring conditions. A decrease in BP at rest while sitting in the morning in the laboratory was significant for diastolic (-5 mm Hg, p less than 0.01) but not for systolic BP. During exercise, systolic BP was significantly lower after training, when measured at the same submaximal workloads. However, when workload was expressed as a percentage of peak oxygen uptake, systolic BP was not different before and after training. When measured during 24 hours, the training-induced change in BP was not significant at night either for systolic or diastolic BP. During the day the decrease in diastolic BP was significant (-5 mm Hg, p less than 0.001), but the change in systolic BP was not.

Adult↗
PubMed1989

The lymphocyte-specific protein tyrosine kinase p56lck is hyperphosphorylated on serine and tyrosine residues within minutes after activation via T cell receptor or CD2.

Human T cells can be activated and induced to proliferate through either the antigen-specific receptor complex (TcR-CD3) or the CD2 surface molecule. Following stimulation, both serine and tyrosine phosphorylation of cellular protein have been demonstrated to occur. p56lck, a protein tyrosine kinase associated to the inner face of the plasma membrane, is almost exclusively expressed in lymphoid cells, especially T cells. Within minutes after activation of a human T cell-derived line (Jurkat) via stimulation of either the TcR-CD3 complex or the CD2 glycoprotein, we observed a hyperphorphosylation of p56lck. A concomitant shift to a higher molecular weight in sodium dodecyl sulfate-polyacrylamide gel was also observed. Similar changes were obtained with phorbol 12-myristate 13-acetate. Tryptic phosphopeptide analysis of the hyperphosphorylated form of p56lck yielded new phosphorylated sites in serine residues and an increased tyrosine phosphorylation. These results suggest that p56lck may be intimately connected to the signaling pathway in T cell activation.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

Humoral and cellular effects of the K(+)-channel activator cromakalim in man.

The effect of cromakalim, a K(+)-channel activator, on the plasma renin-angiotensin-aldosterone system, catecholamines and alpha-atrial natriuretic peptide, and on the intraerythrocyte concentration and transmembrane fluxes of Na+ and K+ has been investigated in 18 normal male subjects, in a double-blind parallel study. After a run-in period on placebo for 1 week, the subjects were treated either with placebo (n = 6) or cromakalim (n = 12) for 1 week. Plasma renin activity was significantly increased during cromakalim. No effect of cromakalim on plasma angiotensin II, aldosterone, adrenaline, noradrenaline and alpha-atrial natriuretic peptide was demonstrated. The intra-erythrocyte K+ concentration was decreased during cromakalim administration and Ca2(+)-dependent K(+)-channels in red blood cells were increased.

Adult↗
PubMed1989

Plasma atrial natriuretic peptide and the renin-aldosterone system during long-term administration of the diuretic xipamide in man.

We have studied the effect of xipamide on plasma alpha-atrial natriuretic peptide and the renin-aldosterone-kallikrein system in twelve healthy men, using a double-blind cross-over design. After a run-in period on placebo for 1 week the subjects were treated with either placebo (n = 6) or xipamide 20 mg once daily (n = 6) for 16 weeks and were then switched to the alternative medication for another 16 weeks. The plasma concentration of alpha-atrial natriuretic peptide fell after 1 week of xipamide administration and increased during prolonged xipamide administration but remained suppressed. The changes in plasma alpha-ANP observed after 1 week of xipamide were negatively correlated with the changes in haematocrit and haemoglobin. Plasma renin activity (PRA), aldosterone concentration (PAC), and urinary excretion of aldosterone and kallikrein increased after 1 week of xipamide administration, levelled off during the second and fourth weeks, but remained elevated during further prolonged xipamide administration for 16 weeks. The xipamide-induced changes in PRA and PAC were positively correlated with the changes in the haematocrit and haemoglobin. Our data suggest that the changes in plasma renin, aldosterone, and alpha-atrial natriuretic peptide during xipamide administration may be related to diuretic-induced volume contraction.

Aldosterone↗
PubMed1989

Acute calcium entry blockade inhibits the blood pressure but not the hormonal responses to angiotensin II.

The effects of acute calcium entry blockade by isradipine (IS) and placebo (P) on the haemodynamic and humoral responses to angiotensin II (A II) have been compared in two groups of 9 patients with essential hypertension. During 4 sequential periods each of 20 min, an i.v. infusion of A II 0, 2, 4 and 8 ng.kg-1.min-1 was given before (control) and 30 min after the oral administration either of IS or P. After IS, both the blood pressure and the angiotensin II-induced pressor effect were significantly reduced. Isradipine increased the heart rate and this cardio-acceleration was potentiated by A II. In contrast, when A II was infused in the absence of IS, heart rate tended to decrease. IS stimulated plasma renin activity and reduced plasma aldosterone. However, it did not affect either the inhibition of plasma renin activity or the rise in plasma aldosterone in response to A II. In conclusion, acute calcium entry blockade in patients with essential hypertension reduces the pressor response to A II, but not the A II-induced inhibition of renin and increase in plasma aldosterone.

Adrenocorticotropic Hormone↗
PubMed1989

Effect of prolonged physical exercise on intra-erythrocyte and plasma potassium.

The intracellular concentrations of sodium [Na+] and potassium [K+] and the water content in human erythrocytes were investigated in 21 male runners before and after a marathon. From 2 to 5 min after the race, the intra-erythrocyte [K+] was significantly decreased (p less than 0.001) by 7% whereas the plasma [K+], intra-erythrocyte [Na+] and the erythrocyte water content were unchanged. The change in the intra-erythrocyte [K+] observed immediately after the marathon, was negatively correlated with the race time (r = -0.44; p less than 0.05). Furthermore, the change in the plasma [K+] (r = -0.64; p less than 0.001) and the amount of K+ excreted in the urine during the race (r = 0.54; p less than 0.05) were also, respectively, negatively and positively correlated with the race time. It is concluded that during prolonged physical exercise the erythrocytes could serve as a kind of K+ reservoir that is drained with increasing magnitude of body K+ loss. This might explain why in the faster marathon runners, in whom the urinary K+ loss is smaller and the K+ intake is greater than in the slower runners during race, the intra-erythrocyte [K+] is unchanged after a marathon whereas in the slower runners it is decreased.

Adult↗
PubMed1989

Carotid baroreflex sensitivity at rest and during exercise is not influenced by opioid receptor antagonism.

Physical effort involves, along with an increase in the plasma concentration of beta-endorphin, profound cardiovascular adaptations. The aim of the present study was to investigate with the use of the variable neck chamber technique, the influence of the endogenous opioids on the carotid baroreflex control of blood pressure and heart rate at rest as well as during exercise. Ten normal volunteers exercised in the supine position up to 33% and 66% of their maximal exercise capacity and received, in a randomized double-blind cross-over protocol, either saline or naloxone (10 mg intravenously, followed by a continuous infusion of 10 mg.h-1). During exercise a progressive attenuation of the carotid baroreceptor reflex control of blood pressure and heart rate was noted. However, neither at rest nor during exercise, did opioid antagonism influence the carotid baroreceptor control of blood pressure and heart rate. Intra-arterial pressure and heart rate also remained unaffected. In contrast, both at rest and during exercise, naloxone administration produced a significant increase in the plasma concentration of cortisol. The latter suggests that in vivo the opioid receptors were effectively antagonized. In conclusion the present study confirms that opioids play only a minor role in cardiovascular homeostasis at rest. In addition, this study demonstrates that they are not involved in the cardiovascular adaptation to exercise, nor in the exercise-related attenuation of the carotid baroreceptor control of pressure and heart rate.

Adult↗
PubMed1989

Left ventricular dynamics during exercise in elite marathon runners.

To assess left ventricular structure and function at rest and during exercise in endurance athletes, 10 elite marathon runners, aged 28 to 37 years, and 10 matched nonathletes were studied by echocardiography and supine bicycle ergometry. Each athlete's best marathon time was less than 2 h 16 min. Echocardiography was performed at rest, at a 60 W work load and at an individually adjusted work load, at which heart rate was 110 beats/min (physical working capacity 110 [PWC110]). Oxygen uptake at PWC110 averaged (+/- SD) 1.14 +/- 0.2 liters/min in the nonathletes and 2.0 +/- 0.2 liters/min in the runners (p less than 0.001). The left ventricular internal diameter at end-diastole was similar at the three activity levels in the control subjects but increased significantly from rest to exercise in the runners (p less than 0.001). Left ventricular systolic meridional wall stress remained unchanged during exercise in the nonathletes but was significantly higher at PWC110 in the athletes (p less than 0.05). Both the systolic peak velocity of posterior wall endocardial displacement and fractional shortening of the left ventricular internal diameter increased with exercise; at PWC110 the endocardial peak velocity was higher in the runners than in the control subjects (p less than 0.01). The endocardial peak velocity during relaxation was comparable in athletes and control subjects at rest, increased similarly at a 60 W work load, but was higher in the runners at PWC110 (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Body weight, sodium intake and blood pressure.

The aim of the present review is to examine the evidence that blood pressure may be reduced and hypertension prevented by decreasing body weight and sodium consumption. Cross-sectional and longitudinal population studies, and intervention studies in individual subjects, suggest that hypertension can be prevented by avoiding excessive weight. Children and adolescents should particularly avoid becoming overweight as this is strongly associated with hypertension in adult life. In contrast, the hypothesis that hypertension might be reduced by restricting sodium intake is less convincing. Moreover, the amount of sodium restriction needed to significantly reduce blood pressure might make it a less practical preventative measure in the struggle against hypertension than weight loss.

Blood Pressure↗
PubMed1989

Changes in potassium content and membrane potassium channels in circulating cells from normal volunteers treated with cromakalim.

The effect of cromakalim, a K+-channel activator, on the intracellular concentration and transmembrane fluxes of Na+ and K+, was studied in 18 normal male subjects, using a double-blind parallel study design. After a run-in period on placebo for 1 week the subjects were treated with either placebo (n = 6) or cromakalim (n = 12) for 1 week. Blood pressure was not changed during cromakalim administration in these normal male subjects but heart rate was increased. The intraerythrocyte and intraleucocyte K+ concentration was decreased during cromakalim administration while the Ca2+-dependent K+ channels in the red blood cells were increased. No significant effect of cromakalim could be demonstrated on the intracellular Na+ and Mg2+ concentration, on the ouabain-sensitive or bumetanide-sensitive 86Rb uptake and on the maximal 3H-ouabain binding in erythrocytes and leucocytes. The red cell Na+Li+ countertransport, anion carrier and ground membrane leak of Na+ and K+ were also not changed in the cromakalim-treated subjects.

Adult↗