Search PubMed⌕ Search

Biomedical subjects

R Fagard

Publications and source records attributed to R Fagard.

At least 307 records · Page 17Linked to original sources

In vitro effect of xipamide on sodium-potassium transport systems in human erythrocytes.

The in vitro effects of xipamide in a concentration range of 10(-8) to 10(-2) M were investigated on various Na+ and K+ transport systems in human red blood cells. Xipamide inhibited the anion carrier or DIDS-sensitive LiCO3- -influx starting from a concentration of 10(-5) M. However, a decrease in the Na+, K+-pump and the Na+, K+-cotransport activity and a rise in the passive permeability of the cell membrane was only observed starting from a concentration of 10(-4) M xipamide.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Diuretics--a risk in the long-term treatment of hypertensive patients?

The trial of the European Working Party on High blood pressure in the Elderly (EWPHE) revealed an overall decrease in cardiovascular mortality and morbidity in the actively treated patients. They received as first-line drugs a combination of hydrochlorothiazide and triamterene; methyldopa was added as necessary. The present post hoc analysis examined the effect of the diuretic treatment on cardiovascular events, both when given alone and in conjunction with methyldopa, by calculating the relative hazard rates (RHR) for cardiovascular mortality and morbidity. Using the Cox proportional hazard model, compared with placebo, a 34% reduction in cardiovascular mortality in the intention-to-treat analysis was demonstrated in the diuretic (hydrochlorothiazide and triamterene) group with an RHR of 0.66 and a 95% confidence interval (CI) of 0.44-0.97; the 16% decrease in the group treated with diuretics and methyldopa was not significant (RHR, 0.84; 95% CI, 0.56-1.25). The effect of treatment in the latter combined group became significant (RHR, 0.62; 95% CI, 0.40-0.95) when all cardiovascular study terminating events were considered; they were reduced by 38%. No effect of treatment on mortality from all causes was detected.

Aged↗

Obesity and hypertension.

In adults of Western societies the positive relationship between blood pressure and body weight has often been demonstrated, both cross-sectionally and longitudinally. This correlation is even stronger in children and early adulthood. In most studies in children, the association between age and blood pressure disappears after controlling for weight. Association must be differentiated from causation. It has however been shown in several intervention studies that treatment of obesity by weight loss decreases blood pressure substantially both in hypertensive and normotensive subjects. Although combining results from several intervention trials is difficult this is the only practical way to get an overall estimate of the hypotensive response to be expected from weight reduction. In the studies presently reviewed, a decrease in weight by 1 kg resulted in a reduction in blood pressure by 3.4/1.3 mm Hg in hypertensive patients and in normotensive subjects the corresponding reductions averaged 1.4 mm Hg and 0.6 mm Hg for systolic and diastolic pressure, respectively.

Animals↗

Implications of the main therapeutic trials conducted in hypertension.

An impressive number of patients has been followed in intervention trials, some of them carefully designed and executed. The different intervention trials in hypertensives are compatible with the hypothesis that hypotensive drug treatment can decrease cardiovascular mortality mainly by decreasing cerebrovascular mortality. A decrease in fatal and non-fatal cardiovascular event rate is mainly due to the decrease in cerebrovascular events. On the basis of these trials the expert committee of the WHO and ISH recommend first general hygienic measures. When the blood pressure remains above 100 mm Hg after 3 months or above 95 mm Hg after 6 months follow-up, hypotensive drugs should be considered. It is not established whether the hypotensive drug treatment is advisable in: --symptomless patients with isolated systolic hypertension, --hypertensive patients above age 80. Sudden reduction in blood pressure should be avoided but whether a progressive reduction of the systolic blood pressure below 140 mm Hg and a diastolic blood pressure below 85 mm Hg is dangerous or advantageous remains to be established.

Adult↗

Maximum oxygen uptake and cardiac size and function in twins.

The contribution of heredity to the interindividual variability of maximum oxygen uptake and of cardiac size and function of healthy male twins, age 18 to 31 years, was studied to evaluate the role of the heart in the inheritance of aerobic power. Twelve pairs of monozygotic and 12 pairs of dizygotic twins were examined. Weight (p less than 0.05), relative weight (Quetelet index) (p less than 0.01) and skinfold thickness (p less than 0.01) were found to be genetically determined, as well as heart rate at rest (p less than 0.05) and systolic blood pressure (p less than 0.05). Genetic variation was significant (p less than 0.05) both for absolute and for weight-adjusted oxygen uptake, measured at peak exercise on the bicycle ergometer. However, the influence of inheritance on aerobic power was not associated with a significant genetic effect on the end-diastolic left ventricular internal diameter or on its fractional shortening as assessed by echocardiography. Genetic variation had a significant (p less than 0.05) effect on left ventricular mass, but this could be attributed to the inheritance of body size. These data indicate that cardiac factors are not significantly involved in the inheritance of aerobic power and suggest that cardiac hypertrophy in athletes is secondary to training.

Adolescent↗

Correlation between phosphorylation and kinase activity of a tyrosine protein kinase: p56lck.

P56lck is the product of a cellular oncogene highly expressed in lymphoid cells. Tyrosine kinase activity was measured by using an exogenous substrate: polyamino acid glutamic acid-tyrosine (4:1) (PGT). Different levels of phosphorylation of p56lck were achieved by the utilisation of SH reagents and different lengths of incubation time. The phosphorylation of PGT was proportional to the level of phosphorylation of p56lck. Identical results were obtained with crude membrane preparations and with p56lck partially purified on immunecomplexes.

Adenosine Triphosphate↗

The amino terminal region of the p56 lck from LSTRA exerts negative modulation on the tyrosine kinase activity.

High levels of tyrosine kinase activity have been detected in the murine lymphoma LSTRA (p56). The functional domains of this kinase have been studied by the use of antibodies generated against peptides from the amino terminal region and from the tyrosine autophosphorylation site. The amino terminal antibody had higher affinity for the p56 than the antibody directed against the phosphotyrosine site. However, the phosphorylation of exogenous substrate by p56 was lower when the tyrosine kinase was immunocomplexed by the antibody against the amino terminal region than when the kinase was complexed by the phosphorylation site antibody. This suggests that in the N-terminal region exist structures which modulate the tyrosine kinase activity of the p56.

Animals↗

Acute haemodynamic and humoral responses to felodipine and metoprolol in mild hypertension.

Oral administration of felodipine to 10 patients with mild essential hypertension acutely reduced systemic vascular resistance (SVR) by 40% after 30 min. The change in SVR was significantly related to age (r = -0.74). The reduction in the intraarterially measured brachial artery pressure was limited to 15/13 mmHg, due to a rise in cardiac output (CO). The tachycardia was sustained for 90 min, as was an elevation of plasma noradrenaline. There was a transient increase in stroke volume, associated with a reduction in pulmonary capillary wedge pressure, which was at least partly due to a reduced intravascular volume. In contrast to SVR, pulmonary vascular resistance was not affected by felodipine. Addition of intravascular metoprolol after 90 min decreased HR and CO and augmented SVR. The felodipine-induced rise in plasma renin activity (PRA) of 100% was completely reversed by metoprolol. Plasma angiotensin II (PA II) rose by 15% during felodipine, whereas plasma aldosterone concentration (PAC) was not affected. Thus, acutely administered felodipine was a potent dilator of systemic but not of pulmonary arterioles, it stimulated the sympathetic nervous system, and reduced left ventricular filling pressure. The rise in plasma renin did not result in a higher plasma aldosterone level, due partly to reduced generation of angiotensin II.

Adult↗

Calcium, vitamin D-endocrine system, and parathyroid hormone in black and white males.

The serum and urinary calcium, 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), and parathyroid hormone (PTH) were studied in healthy black and white males living in Belgium, and the results were compared to data in blacks of similar age living in Zaïre. Dietary calcium and vitamin D were estimated in a sub-sample of blacks and whites examined in Belgium. Compared to whites (9.51 +/- 0.28 mg%) serum calcium was somewhat lower in blacks (9.26 +/- 0.27 mg% in Belgium; 9.19 +/- 0.48 mg% in Zaïre). The 24 hour urinary calcium excretion averaged 215.0 +/- 16.7 mg% in whites and was higher (P less than 0.05 or less) than in blacks (115 +/- 71 mg% in Belgium; 36 +/- 33 mg% in Zaïre). The serum 25OHD levels were similar in whites and blacks evaluated in Zaïre, both being higher (P less than 0.05 or less) than in blacks living in Belgium. In the latter blacks, an inverse correlation was observed between the 25OHD level and the duration of the stay in a temperate climate. Parathyroid hormone levels were slightly higher in blacks living in Belgium than in the other two groups of subjects. The serum levels of 1,25(OH)2D3 and human vitamin D-binding protein were similar in the three groups of subjects. Dietary calcium averaged 541 +/- 152 mg/day in blacks and was significantly (P less than 0.001) less than in whites (1,203 +/- 508 mg/day), whereas no significant difference was observed in dietary vitamin D intake between blacks and whites. It is concluded that calcium intake is low in blacks but stimulation of parathyroid hormone and 1,25(OH)2D3 required to achieve normocalcemia does not occur.

25-Hydroxyvitamin D 2↗

Progressive attenuation of the carotid baroreflex control of blood pressure and heart rate during exercise.

With the use of a variable pressure neck chamber, the effect of supine bicycle exercise on the carotid baroreceptor reflex was investigated in 10 normal volunteers who were studied at rest and during moderate and severe exercise, i.e., at 33% and 66% of their previously determined maximal exercise capacity. Deactivation of the carotid baroreceptors by a decrease in carotid transmural pressure produced a greater (p less than 0.001) increase in mean intra-arterial pressure at rest (+11.2 +/- 0.2 [SE] mm Hg) than during moderate (+9.0 +/- 0.2 mm Hg) and severe (+6.1 +/- 0.1 mm Hg) exercise. Heart interval decreased less (p less than 0.005) at rest (-73 +/- 3.2 msec) than during exercise (-0.7 +/- 0.7 msec and -4.6 +/- 0.2 msec, respectively). Furthermore, activation of the carotid baroreceptors by an increase in carotid transmural pressure provoked a greater (p less than 0.005) reduction in mean intra-arterial pressure at rest (-11.5 +/- 0.2 mm Hg) than during exercise (-9.8 +/- 0.1 mm Hg and -7.5 +/- 0.1 mm Hg, respectively), while the lengthening of heart interval was also more (p less than 0.005) pronounced at rest (+97 +/- 4.3 msec) than during moderate (+44 +/- 1.2 msec) and severe (+7.6 +/- 0.3 msec) exercise. Finally, carotid baroreceptor sensitivity was defined as the slope of the changes in blood pressure and heart interval that occurred with increasing (baroreceptor deactivation) and decreasing (activation) neck tissue pressure. On average, baroreceptor sensitivity was consistently smaller (p less than 0.05) during exercise, as compared to rest.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Assessment of stiffness of the hypertrophied left ventricle of bicyclists using left ventricular inflow Doppler velocimetry.

Sixteen male bicyclists and 16 control subjects were studied to assess whether the left ventricular hypertrophy of athletes is associated with changes in diastolic left ventricular function. The cyclists had a larger left ventricular internal diameter on echocardiography (55.2 versus 47.9 mm; p less than 0.001) and a disproportionate increase in wall thickness relative to the internal diameter (0.48 versus 0.41; p less than 0.01), indicating a mixed eccentric-concentric type of hypertrophy. Left ventricular inflow Doppler velocimetry showed similar results in athletes and control subjects for peak flow velocities in the atrial contraction phase (30 versus 32 cm/s; p = NS) and in the early diastolic rapid filling phase (71 versus 67 cm/s; p = NS). The similar ratio of both velocities, that is, 0.43 in the cyclists and 0.49 in the control subjects, suggests that left ventricular distensibility is unaltered in cyclists. It is concluded that the left ventricular hypertrophy observed in cyclists is not associated with changes in ventricular stiffness, as estimated from left ventricular inflow Doppler velocimetry.

Adolescent↗

Calcium entry blockade or beta-blockade in long-term management of hypertension in blacks.

The long-term efficacy of nitrendipine and acebutolol was assessed during a 40-week double-blind randomized trial in 60 hypertensive blacks. Nitrendipine (mean dose 32 mg/day) and acebutolol (414 mg/day) were administered in monotherapy in increasing dosage and mefruside was added in patients not controlled by monotherapy. The recumbent and standing blood pressures were reduced (P less than 0.01 or less) during monotherapy with nitrendipine and acebutolol, but the magnitude of blood pressure reduction was greater (P less than 0.05 or less) during nitrendipine dosing. Pulse rate decreased (P less than 0.01) during acebutolol whereas nitrendipine induced a nonsignificant increase. Both treatments induced no changes in serum electrolytes, creatinine, urea, uric acid, lipids, plasma renin activity, and plasma and urinary aldosterone. The overall incidence of side effects was similar with both treatments but four patients discontinued nitrendipine because of headache. The addition of mefruside to nitrendipine or acebutolol produced a further fall of blood pressure in patients not controlled with monotherapy. Monotherapy with nitrendipine or acebutolol offers an effective, safe first-line antihypertensive treatment in blacks entered in this study; with the described dosages and therapeutic schedule, nitrendipine was somewhat more effective than acebutolol.

Acebutolol↗

Noninvasive assessment of systolic and diastolic left ventricular function in female runners.

Nine female runners and 9 matched control subjects were investigated with echocardiography and Doppler velocimetry to assess cardiac structure and systolic and diastolic left ventricular (LV) function at rest. LV mass was considerably larger in the athletes (171 vs 123 g; P less than 0.01). Minute distance, the Doppler index of cardiac output, was similar in runners and controls; the lower heart rate (P less than 0.01) of the athletes was associated with a higher stroke distance (P less than 0.05). The latter could be attributed to a larger end-diastolic LV internal diameter (46 vs 43 mm; P less than 0.05); wall stress and the various indices of systolic LV function were not different between runners and controls. Early diastolic LV function, estimated from the velocity of LV relaxation and the LV inflow pattern, and late diastolic function, assessed by Doppler velocimetry, were similar in runners and controls. The unchanged ratio of the peak velocities of LV filling during atrial contraction and early filling (0.49 vs 0.44; NS) indicates that LV distensibility is unaltered in the athletes. In conclusion, the higher left ventricular mass of female runners is not associated with changes of systolic and diastolic LV function.

Cardiac Volume↗

Mechanism of hypotensive action of ketanserin in men.

The mechanism of the hypotensive action produced by ketanserin during chronic treatment in humans remains unknown. In contrast to previous reports, recent data show that ex vivo inhibition of the serotonin-induced platelet aggregation can be demonstrated in men during chronic ketanserin administration, provided that the pH is controlled in the in vitro assay. This test could be used as a tool to measure the degree of serotonin inhibition, at least at the platelet level.

Antihypertensive Agents↗

The use of Doppler echocardiography to assess the acute haemodynamic response to felodipine and metoprolol in hypertensive patients.

In order to evaluate the use of Doppler echocardiography in the assessment of the haemodynamic effects of antihypertensive drugs, the acute haemodynamic response to felodipine and additional administration of metoprolol after 90 min was assessed in 10 hypertensive patients, by using both the Fick method and Doppler blood flow velocimetry in the ascending aorta. Intrabrachial artery pressure was significantly reduced by the treatment. Both the Fick and Doppler estimates of cardiac output (CO) rose significantly with felodipine and reached their highest values after 30 min, 45 +/- 8% (s.e.m.) and 58 +/- 7%, respectively. The felodipine-induced increase of heart rate (HR) persisted for 90 min, but the increase of stroke volume was only transient. Metoprolol brought CO and HR back to control levels. The felodipine- and metoprolol-induced changes of CO and stroke volume (SV) from control were on average not different between the observations with the Fick and the Doppler techniques throughout the study. As for the absolute values (control period), the Doppler measurement under-estimated SV (10 ml) and CO (1.1 l/min) in comparison with the Fick method, and the limits of agreement (mean difference +/- 2 s.d.) between both methods were 42 and -22 ml for stroke volume and 3.4 and -1.2 l/min for CO. In conclusion, despite the poor agreement in absolute results between the two methods, aortic Doppler velocimetry reflects the acute haemodynamic changes induced by felodipine and metoprolol in a group of hypertensive patients. The technique should facilitate the study of haemodynamic effects of drugs in man.

Adult↗

Correlates of blood pressure in rural and urban Zaïre.

Blood pressure and anthropometric characteristics were studied in 312 rural and 675 urban Bantu of Zaïre aged 10 years and more; proteinuria and the urinary sodium to potassium ratio were determined. On average, systolic and diastolic pressure were higher in rural than in urban Bantu, and rose with advancing age in both populations. However, rural Bantu were older, lighter and smaller, and had a lower sodium:potassium ratio than urban Bantu. Using multiple regression analysis, systolic and diastolic pressures correlated positively with age, weight, pulse rate, sex and sodium:potassium ratio; diastolic pressure also correlated negatively to height. After adjusting blood pressure for these independent correlates, systolic pressure remained significantly higher in rural Bantu. However, no significant difference persisted between the two populations after adjusting blood pressure for age alone. The prevalence of hypertension in rural and urban Bantu increased with age and was 14.2 and 9.9%, respectively, for participants at least 20 years old; women were more affected in the rural area, whereas men were more affected in the urban population. The occurrence of proteinuria was higher in rural Bantu than in urban; it was similar in participants with and without definite hypertension. It is suggested that higher blood pressure in the rural setting was mostly accounted for by the older age of the population.

Adolescent↗

Serum cholesterol during ketanserin and propranolol administration in hypertensive patients.

The effect of ketanserin and propranolol on the serum total cholesterol (TC), and high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) cholesterol was studied in hypertensive patients treated for 3 months. During ketanserin administration, LDL-C decreased, whereas HDL-C and the HDL-C/LDL-C ratio increased and no significant effect in serum total cholesterol occurred. During propranolol administration, no significant effect was observed on serum total cholesterol, HDL-C and LDL-C, but the ratio of HDL-C/LDL-C increased. Intergroup comparison showed a greater increase in HDL-C (p less than 0.05) and in the HDL-C/LDL-C ratio (p less than 0.01) in the ketanserin group as compared with the propranolol group.

Body Weight↗