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Biomedical subjects

R Fagard

Publications and source records attributed to R Fagard.

At least 271 records · Page 15Linked to original sources
PubMed1989

Effects of the new calcium entry blocker isradipine (PN 200-110) in essential hypertension.

In this double-blind cross-over study 16 patients with mild-to-moderate hypertension were treated with placebo and the dihydropyridine derivative, isradipine 5-10 mg twice daily. In the supine position isradipine reduced systolic (-18 mm Hg; p less than 0.002) and diastolic (-15 mm Hg; p less than 0.001) pressures, while heart rate was not changed; in the standing position, systolic (-15 mm Hg; p less than 0.002) and diastolic (-14 mm Hg; p less than 0.001) pressures decreased, whereas heart rate increased (+6 bpm; p less than 0.05). Body weight and lower leg volumes remained unaltered, suggesting that isradipine did not cause fluid retention. On IS plasma angiotensin I (+40 pg/ml), angiotensin II (+ 14 pg/ml), and aldosterone (+4.1 ng/dl) rose. The intracellular Na+ and K+ concentrations and the transmembrane cation transport activities (Na+-K+ pump, Na+-K+ cotransport, Na+-Li+ countertransport), measured ex vivo in the erythrocytes of eight male patients, were not significantly influenced by isradipine. Hot flushes and facial erythema occurred more frequently (p less than 0.05) on isradipine than on placebo. In conclusion, the new calcium entry blocker isradipine at a dose of 5-10 mg twice daily lowers blood pressure and is well tolerated in most patients with essential hypertension.

Blood Pressure↗
PubMed1989

Long-term double-blind comparison of doxazosin and atenolol in patients with mild to moderate hypertension.

The antihypertensive effect and safety of doxazosin once daily as well as the effect on serum lipids was compared with that of atenolol once daily in 40 patients with mild to moderate hypertension. During the first 4 weeks, all patients received placebo therapy. During the subsequent 46 weeks, patients were randomized to doxazosin or atenolol treatment. Treatment was initiated with 1 mg doxazosin or 50 mg atenolol once daily. The dose could be doubled biweekly for 10 weeks until a final dose of 16 mg doxazosin or 100 mg atenolol was reached. The patients then entered the maintenance phase for 36 weeks. The average final dose of doxazosin was 9.2 +/- 1.3 (SEM) mg and that of atenolol was 76.5 +/- 6.2 mg. During the 46 weeks of active treatment, the recumbent diastolic blood pressure (DBP) tended to be lower (p less than 0.05) in patients receiving atenolol at 10, 12, and 22 weeks of treatment. Recumbent systolic BP (SBP) and standing SBP and DBP were not different, however, between patients receiving doxazosin and those receiving atenolol. Recumbent and standing heart rate (HR) were lower (p less than 0.01) during atenolol. The decrease in serum total triglycerides, total cholesterol, and low-density lipoprotein (LDL)-cholesterol after 46 weeks of doxazosin was different (p less than 0.05) from the changes observed during atenolol therapy. Our data indicate that the antihypertensive action of doxazosin is accompanied by favorable effects on serum lipids.

Adult↗
PubMed1989

Effect of verapamil on systemic and brachial artery hemodynamics in normal humans: comparison with effect of atenolol.

To clarify the hemodynamic effects of verapamil, we investigated in normal volunteers the effects of 4-day treatment with verapamil (240 mg/day) on left ventricular function and on systemic and brachial artery haemodynamics, in comparison with the effects of placebo and atenolol (100 mg/day). Left ventricular structure and function was evaluated by echocardiography, systemic hemodynamics were assessed by pulsed Doppler velocimetry of the ascending aorta, and brachial artery hemodynamics were assessed pulsed Doppler velocimetry of the brachial artery. Verapamil decreased systemic and brachial artery vascular resistance (p less than 0.05), increased cardiac output (CO, p less than 0.01) and brachial flow (p = 0.054), and did not affect blood pressure (BP) and heart rate (HR). In contrast, atenolol decreased BP, HR, and CO (p less than 0.001) but did not significantly affect brachial flow and systemic and brachial artery vascular resistance. We conclude that short-term administration of verapamil in normal humans produces systemic and brachial artery vasodilatation, with a reflex increase of stroke volume but not of HR.

Adult↗
PubMed1989

Elevated level of p60c-src in virus-transformed murine megakaryocytic cell lines.

Megakaryocytic cell lines derived from mouse bone marrow cells transformed by the Myeloproliferative Leukemia Virus (MPLV) contain elevated levels of p60c-src. Northern blot analysis revealed the presence of a 4 kb normal sized c-src transcript only in MPLV-transformed megakaryocytic cell lines containing a high percentage of acetylcholinesterase positive cells (AChE+ greater than 10%), but not in MPLV-transformed erythroblastic or myeloblastic cell lines. The p60c-src protein was identified in lysates from in vivo labelled cells and in in vitro labelled membrane extracts by immunoblotting analysis and by immunoprecipitations with specific anti-src antibodies. In dimethylsulfoxide (DMSO) treated cells, the number of AChE+ cells increased together with p60c-src kinase activity indicating a possible correlation between p60c-src expression/activity and megakaryocytic differentiation.

Acetylcholinesterase↗
PubMed1989

Isolated systolic blood pressure elevation in the elderly: mechanisms, risk, and the need for further studies.

Isolated systolic hypertension (ISH) is generally defined as a systolic pressure of 160 mm Hg or more, with a diastolic pressure cutoff point below 95 mm Hg in some studies and 90 mm Hg in others. Its prevalence and incidence vary from 3 to 30% depending on the definition applied, methodology of measurement, as well as the population and the age and sex of the patient. Mechanisms that could lead to the development of isolated systolic hypertension are discussed, especially the role of atherosclerosis. The risks of systolic hypertension on mortality and morbidity in the elderly are considered. The need for further studies to quantify the risk and the effect of treatment is emphasized. The Syst-Eur trial enters patients above the age of 60 years with a diastolic pressure below 95 mm Hg and a systolic of 160 mm Hg or more. The study is a double-blind, placebo-controlled trial and the main purpose is to examine the influence of ISH on morbidity, mortality, and general well-being. Investigation of blood pressure variation over 24 h and its relationship to morbidity and use for planning treatment will be incorporated. Other centers are invited to join in the enlarging project.

Adult↗
PubMed1989

Converting enzyme inhibitors in the treatment of elderly hypertensives.

Angiotensin-converting enzyme inhibitors are gaining acceptance as safe and effective agents for treatment of hypertension. Addressed in this review of the available literature are the questions whether they are effective in lowering blood pressure in the elderly, whether their effects are age-related, and what effects, if any, do they have on morbidity and mortality in geriatric hypertension.

Aged↗
PubMed1989

The influence of menopause on blood pressure.

The association between menopause and systolic and diastolic blood pressure was explored in a random sample of 278 pre- and 184 post-menopausal women. In 64 subjects menopause had been surgically induced. Post-menopausal women had a higher systolic, diastolic and pulse pressure than pre-menopausal subjects (P less than 0.001). Hypertension, defined as being on antihypertensive medication, regardless of BP, or as having a pressure greater than or equal to 140/90 mmHg, was more frequently observed following menopause (40 vs 10%; P less than 0.001). After stratification by age and body mass index, the odds of having hypertension for pre- as compared with post-menopausal women were 2.2 (95% confidence interval from 1.1 to 4.4; P = 0.03). After adjustment of BP for significant covariates, such as body mass index, pulse rate and contraceptive pill intake, the slope of SBP on age was 0.5 mmHg/year (P less than 0.05) steeper in women with natural and surgical menopause than in pre-menopausal subjects. The relation of DBP with age showed a similar slope among pre- and post-menopausal subjects, but in women with natural and surgical menopause taken together, the regression line was shifted upward by an average of 2.3 mmHg (P = 0.03). The relationships of DBP with body mass index and with the urinary sodium: potassium ratio were also 0.2 mmHg/kg/m2 and 0.8 mmHg/unit steeper (P less than 0.05) in post- than in pre-menopausal subjects. In conclusion, in the present cross-sectional study menopause was accompanied by a steeper rise of SBP with age, and by an increase in the absolute level of DBP, which was independent of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

[The influence of menopause on blood pressure].

The association between menopause and systolic and diastolic blood pressure was explored in a random sample of 278 pre- and 184 post-menopausal women. In 64 subjects menopause had been surgically induced. Post-menopausal women had a higher systolic, diastolic and pulse pressure than pre-menopausal subjects (p greater than 0.001). Hypertension, defined as being on antihypertensive medication, regardless of blood pressure, or as having a pressure greater than or equal to 140/90 mmHg, was more frequently observed following menopause (40 vs 10%; p greater than 0.001). After stratification by age and body mass index, the odds of having hypertension for pre- as compared with post-menopausal women were 2.2 (95% confidence interval from 1.1 to 4.4; p = 0.03). After adjustment of blood pressure for significant covariates, such as body mass index, pulse rate and contraceptive pill intake, the slope of systolic pressure on age was 0.5 mmHg/year (p less than 0.05) steeper in women with natural and surgical menopause than in pre-menopausal subjects. The relation of diastolic blood pressure with age showed a similar slope among pre- and post-menopausal subjects, but in women with natural and surgical menopause taken together, the regression line was shifted upward by an average of 2.3 mmHg (p = 0.03). The relationships of diastolic blood pressure with body mass index and with the urinary sodium: potassium ratio were also 0.2 mmHg/kg/m2 and 0.8 mmHg/unit steeper (p less than 0.05) in post- than in pre-menopausal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

[Sympathetic modification of the relationship between salt intake and blood pressure in the general population].

Using pulse rate and urinary sodium as indices of sympathetic tone and salt intake, respectively, we investigated whether both an increased sympathetic activity and a high salt consumption are needed to increase blood pressure in the population at large. A random population sample of 2081 subjects with a minimum age of 18 years was stratified by tertiles of pulse rate. In subjects with a slow and in those with a fast pulse rate, a significant curvilinear relation between blood pressure and urinary sodium was found, while in the middle pulse rate third the correlation was not significant. A significant interaction between pulse rate and urinary sodium indicated that, when urinary sodium increased from 160 to 300 mmol/24 h, both systolic and diastolic pressure rose in subjects with a fast pulse rate, but declined in those with a slow pulse rate. In conclusion, our results suggest that a high salt intake is associated with an elevated blood pressure in subjects with a high sympathetic tone, but with a decreased pressure in individuals with a low sympathetic activity.

Blood Pressure↗
PubMed1989

Possible biochemical mechanisms involved in the antihypertensive drug-induced changes in serum lipoproteins.

The antihypertensive drug-induced changes in serum lipoproteins can be attributed to two major mechanisms, namely an increased hepatic lipoprotein synthesis and a disturbed lipoprotein catabolism. Thiazides, by inhibiting phosphodiesterase, increase the intracellular concentration of cyclic AMP leading to a stimulation of lipolysis. beta-Blockers may reduce the adenylate cyclase activity in liver cells, leading to a reduced inhibition of the liver triglyceride synthesis and a higher secretion of VLDL triglyceride particles. alpha-Blockade through phosphodiesterase inhibition and an increased cAMP level, can result in a blockade of the liver triglyceride synthesis and a reduced serum triglyceride concentration. Lipoprotein lipase activity is reduced by beta-blockers and stimulated by alpha-blockers, leading, respectively, to a lower and a higher plasma HDL cholesterol. Besides these two major mechanisms, a direct effect of antihypertensive drugs on intracellular cholesterol synthesis can also be postulated.

Animals↗
PubMed1988

The pulmonary circulation in essential systemic hypertension.

Seventy-one men, ages 16 to 59 years, were referred for systemic hypertension, which was without detectable cause and with limited organ damage (World Health Organization stages I to II). They performed a graded exercise test on the bicycle ergometer in the sitting position. Mean brachial intraarterial pressure, mean pulmonary artery and wedge pressures and cardiac output (Fick method) were measured. At rest mean brachial artery pressure ranged from 72 to 168 mm Hg. Mean pulmonary wedge pressure was significantly (p less than 0.05) related to mean brachial artery pressure at rest, at submaximal work (50 watts) and at the end of exercise (161 +/- 42 [standard deviation] watts). In each subject pulmonary vascular resistance was calculated as the slope of the relation between the pressure gradient across the pulmonary circulation and cardiac output from data at rest, at 50 watts and at the end of exercise; mean critical closing pressure was calculated as the intercept of this relation. Pulmonary vascular resistance averaged 0.63 +/- 0.37 mm Hg/liter/min and was significantly related to age (r = 0.28, p less than 0.05) but not to rest brachial artery pressure (r = 0.14) or pulmonary wedge pressure (r = 0.09, difference not significant for both). The mean critical closing pressure averaged 6.1 +/- 4.0 mm Hg and was not related to brachial artery pressure (r = -0.08) or to age (r = -0.18, difference not significant for both). It is concluded that there is neither a primary nor a secondary effect of systemic hypertension on the pulmonary vasculature in patients with World Health Organization stages I to II essential hypertension.

Adolescent↗
PubMed1988

Purification of the LSTRA tyrosine protein kinase (p56lck).

p56lck, a p60src related tyrosine protein kinase was recently described in a murine lymphoma cell line (LSTRA), in several human lymphomas and in normal peripheral lymphocytes. We have purified p56lck to homogeneity by electrofocusing followed by two-step SDS/polyacrylamide gel electrophoresis. The pure protein was identical to the p56 characterized in LSTRA cells and used to raise antibodies in rabbits. This simple procedure is applicable for the rapid purification of minor proteins.

Amino Acids↗
PubMed1988

Erythrocyte, plasma and urinary magnesium in men before and after a marathon.

Erythrocyte, plasma and urinary magnesium (Mg2+) concentration was measured in 23 runners before and after a marathon race. Blood samples were drawn from an antecubital vein the morning before the race (baseline), at 3 p.m. (2 h before the start), upon finishing and 12 h later. Compared with the baseline values, the intra-erythrocyte and plasma Mg2+ were decreased (p less than 0.05 or less) immediately after the marathon, from 2.13 +/- 0.16 to 2.02 +/- 0.18 mmol.l-1 cells and from 0.88 +/- 0.06 to 0.81 +/- 0.07 mmol.l-1 respectively. The Mg2+ concentration returned to pre-race values 12 h after completion of the marathon. The urinary Mg2+ excretion rate decreased (p less than 0.001) from 29 +/- 13 to 5 +/- 3 mumol.min-1 during the marathon and increased (p less than 0.05) 12 h after the race to 38 +/- 18 mumol.min-1. It is concluded that the reduction in plasma Mg2+ ion concentration during the marathon cannot be attributed to erythrocyte uptake, urinary excretion or loss in sweat. It is suggested that Mg2+ may be released from erythrocytes into the extracellular fluids during sustained exercise and taken up from these fluids by the adipose cells.

Adolescent↗
PubMed1988

Erythrocyte 2,3-diphosphoglycerate concentration before and after a marathon in men.

Erythrocyte 2,3-diphosphoglycerate (2,3-DPG) concentration was studied in 23 runners before and after a marathon race. Blood samples were drawn from an antecubital vein the morning before the race (baseline), at 3 p.m. 2 h before the start, on finishing, and 12 and 36 h later. Compared to the baseline values, erythrocyte 2,3-DPG concentration was increased (p less than 0.001) immediately after the marathon from 4.62 +/- 0.14 to 5.56 +/- 0.13 mumol.ml-1 RBC and remained elevated 12 h later (5.45 +/- 0.14 mumol.ml-1 RBC): it returned to prerace values 36 h after completion of the marathon.

2,3-Diphosphoglycerate↗
PubMed1988

Effects of training on erythrocyte 2,3-diphosphoglycerate in normal men.

The erythrocyte 2,3-diphosphoglycerate concentration (2,3-DPG) and the activity of red cell hexokinase, pyruvate kinase, glucose-6 phosphate dehydrogenase and glutathione reductase were studied in 27 normal volunteers before and after 2 and 4 months of physical endurance training. The 4 months of training increased maximal oxygen uptake and physical working capacity (PWC130) by 16% (p less than 0.001) and 29% (p less than 0.001) respectively. Resting heart rate was decreased (p less than 0.001) by 11 beats.min-1. With 2 months of training the erythrocyte 2,3-DPG concentration increased by 9% (p less than 0.001); with 4 months training the increase was only 4% (p less than 0.05). The training-induced increase in red cell 2,3-DPG was not accompanied by enhanced activity of erythrocyte hexokinase, pyruvate kinase, glucose-6 phosphate dehydrogenase or glutathione reductase. It is concluded that the rise in red cell 2,3-DPG induced by physical endurance training is not due to activation of red cell glycolytic enzymes or the enzymes involved in the pentose-phosphate cycle.

2,3-Diphosphoglycerate↗
PubMed1988

Effect of calcium channel blockade and beta-adrenoceptor blockade on short graded and single-level endurance exercises in normal men.

The effect of verapamil (240 mg) on exercise capacity was studied during a short graded and a single-level endurance exercise test in 12 normal volunteers; it was compared to the effects of atenolol (100 mg x day-1). Intake of verapamil, atenolol and placebo, administered according to a randomized, double-blind cross-over design, was started 3 days before the exercise tests. Compared to placebo, verapamil did not affect peak oxygen uptake in the graded test or exercise duration in the endurance test. Heart rate, systolic blood pressure, rating of perceived exertion and respiratory data at submaximal and peak exercise were unaffected in either test. On the other hand atenolol reduced maximal oxygen uptake by 5% (p less than 0.001) and endurance exercise duration by 17% (p less than 0.05). Besides marked decreases in heart rate and systolic blood pressure during the two types of exercise, atenolol also reduced oxygen uptake at submaximal exercise levels and it increased the rating of perceived exertion (p less than 0.05), the latter only during the endurance exercise test.

Adrenergic beta-Antagonists↗