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Biomedical subjects

R Fagard

Publications and source records attributed to R Fagard.

At least 361 records · Page 20Linked to original sources
PubMed1985

Hemodynamic response to chronic ketanserin treatment in essential hypertension.

Ketanserin (120 mg/day) or placebo was given orally to 14 patients with mild to moderate essential hypertension according to a double-blind crossover protocol, each treatment period lasting 6 weeks. Resting intraarterial pressure in the recumbent position was reduced from 150/84 to 141/77 mm Hg; the hypotensive effect persisted throughout an uninterrupted graded exercise test to the point of exhaustion. The hemodynamic effects were similar at rest and during exercise. Overall, systemic vascular resistance decreased by 14%, heart rate fell by 5%, but stroke volume and cardiac output increased. The pressor responses to methoxamine and to phenylephrine were reduced by ketanserin.

Adult↗
PubMed1985

Double-blind comparison of ketanserin with propranolol in hypertensive patients: interim report.

This double-blind study, which is still in progress, aims to compare ketanserin (K) and propranolol (P) during long-term treatment of hypertensive patients in general practice. After a run-in period on placebo, active treatment was initiated with 20 mg K or 40 mg P, b.i.d., during a 2-week period, whereafter the daily dose of either drug was doubled. Presently, 331 patients have been randomized, two-thirds to the K group (n = 221) and one-third to the P group (n = 110). Both groups were similar at randomization, with blood pressure (BP) averaging 171/105 mm Hg. The presently available data concerning the initial 3 months of the trial show that up to the 2nd month after randomization, systolic BP was significantly (p less than 0.05) higher in the K than in the P group, whereas the differences in diastolic BP were mostly not significant. The change in BP after 3 months on K treatment was positively and independently related to both the initial BP and the concurrent changes in body weight. Heart rate was lower (p less than 0.001) during P, whereas body weight was not statistically different between both groups. Differences in complaints between the K and P group were small. However, in the K group dry mouth was transiently more frequently reported at 1 month (p = 0.02) and multiple complaints at 3 months (p = 0.03).

Adult↗
PubMed1985

Active and acid-activable inactive renin during inhibition by indomethacin of prostaglandin synthesis in sodium-replete man.

The effect of inhibition of prostaglandin synthesis by indomethacin on active renin and on acid-activable inactive renin was studied in nine healthy, sodium-replete men, both at rest and exercise. These volunteers were investigated after pretreatment with placebo or indomethacin, 150 mg daily for 3 days. Indomethacin induced a decrease in active (P = 0.004), total (P less than 0.001) and inactive (P = 0.02) renin at rest recumbent and at rest, sitting. Inhibition of prostaglandins with indomethacin reduced (P less than 0.001) active and total renin at each level of work load but not (P = 0.32) inactive renin. However the exercise-induced stimulation (P less than 0.05) of active and of total renin still occur during indomethacin. Indomethacin reduced (P less than 0.001) at rest, sitting and at maximal exercise the plasma concentrations of immunoreactive prostaglandins E2, prostaglandin F2 alpha and 13, 14-dihydro-15-keto-prostaglandin F alpha; the urinary excretion of immunoreactive prostaglandin E2 and F2 alpha were also reduced.

Adult↗
PubMed1985

Plasma levels of renin, angiotensin II, and 6-ketoprostaglandin F1 alpha in endurance athletes.

Twelve male runners and 12 matched nonathletes performed a prolonged uninterrupted graded exercise test on the bicycle ergometer up to exhaustion to study blood pressure and plasma levels of renin (PRA), vasoconstrictor angiotensin II (ANG II), and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), a metabolite of the vasodilator prostacyclin. In the athletes work load was increased by 30 W/4 min, and in the control subjects the increments of work load were adjusted to their lower exercise capacity to equalize total exercise duration. Blood was drawn, and blood pressure and O2 uptake (VO2) were measured at rest and at the fourth, eighth, and last steps of exercise. Peak VO2 averaged 60 +/- 1.6 ml . min-1 . kg-1 in the runners and 46.8 +/- 1.5 in the nonathletes. To evaluate differences between athletes and controls, PRA, ANG II, and 6-keto-PGF1 alpha were first adjusted for significant confounding factors, such as age, weight, hematocrit, 24-h urinary sodium excretion, and O2 uptake. PRA was significantly lower in the athletes (F = 11.2; P less than 0.01); ANG II was not different at rest, but its rise with exercise was less steep in the runners (F = 8.2; P less than 0.01), whereas 6-keto-PGF1 alpha was not different between the groups (F = 1.3; NS). Despite the differences in PRA and ANG II, however, blood pressure was similar in athletes and nonathletes (F = 0.0; NS).

6-Ketoprostaglandin F1 alpha↗
PubMed1985

The nature of opioid involvement in the hemodynamic respiratory and humoral responses to exercise.

After 30 min rest in the lying position, 12 healthy male volunteers (average age 22 years) received, in a randomized double-blind cross-over protocol, either saline or naloxone (10 mg iv followed by a continuous infusion of 10 mg/hr). Thereafter they rested for a further 30 min in the recumbent position and for 15 min sitting on a bicycle ergometer; they then exercised to exhaustion. At rest plasma levels of adrenocorticotropin (ACTH), cortisol, and aldosterone increased during infusion of naloxone, while body temperature decreased. During exercise the difference in plasma ACTH between naloxone and saline periods was abolished, while the differences in plasma cortisol and aldosterone lost statistical significance. Intra-arterial pressure, heart rate, ventilation, O2 uptake, and CO2 output were continuously monitored throughout the experiment and were not affected by naloxone. This was also the case for several hormonal and biochemical measurements, including those of plasma renin, angiotensin II, norepinephrine, 13,14-dihydro-15-keto-prostaglandin F2 alpha, glucose and lactate, and serum insulin and growth hormone. Exercise performance was not changed by naloxone. In conclusion (1) during exhaustive graded exercise of short duration opioidergic inhibition of the pituitary-adrenocortical axis is probably not sustained, (2) apart from the latter mechanism, the present study does not support the hypothesis that endogenous opioids are involved in various hemodynamic, respiratory, and hormonal responses to this type of exercise.

Adult↗
PubMed1985

Ketanserin: a new hypotensive drug?

The possible use of ketanserin for the chronic treatment of patients with essential hypertension was discussed based on the data exposed at this symposium. Its hypotensive effect is established during placebo controlled trials, but more data are needed to determine its relative potency compared to standard hypotensive drugs. The drug seems to act by reducing systemic vascular resistance, but the relative role of the serotonin and alpha inhibition in the chronic hypotensive effect in man is not yet known. Subjective side effects occur after the first dose, but seem to be less frequent during chronic treatment; organ toxicity has not been reported in the therapeutic doses. The drug could be particularly indicated in elderly hypertensive patients, especially in those with peripheral vascular disease. The influence on morbidity and mortality is not yet known.

Animals↗
PubMed1985

Intra-erythrocyte concentration and transmembrane fluxes of sodium and potassium during acute and short-term administration of ketanserin in normal male subjects.

The effect of acute and short-term administration of ketanserin on the intracellular concentration and transmembrane fluxes of sodium and potassium in erythrocytes was studied in 12 sodium-replete, normal male subjects. The subjects received 40 mg ketanserin three times a day for one week. Blood samples were drawn before and 2.5 hours after the first dose, 12 hours after the evening dose of the sixth day and 1.5 hours after the morning dose of the seventh day. The intra-erythrocyte sodium concentration was not changed following the first dose of ketanserin, but was decreased (p less than 0.05) during short-term treatment with ketanserin. The ouabain-sensitive 86Rb-uptake, an estimate of the Na+,K+-ATPase pump activity, was decreased (p less than 0.001) after acute ketanserin administration, but not (p = 0.07) during short-term treatment. This change in intra-erythrocyte sodium concentration was related (r = 0.73, p less than 0.01) to the change in ouabain-sensitive 86Rb-uptake. The red cell Na+,K+-cotransport and Na+,Li+-countertransport activity were not changed during acute and short-term administration of ketanserin. The results indicate that short-term ketanserin administration decreases the intra-erythrocyte sodium concentration, but the flux measurements cannot explain this observation.

Adult↗
PubMed1985

Relationship between carotid baroreflex sensitivity, physical fitness and activity in cyclists.

Carotid baroreceptors were stimulated with neck suction in 24 cycling tourists and pulse interval lengthening was measured. Eight intensities of neck chamber suction were applied to select a criterion for computing the RR response that gives a significant linear relationship with the magnitude of the stimuli in the highest number of individuals. The best criterion was the maximal RR prolongation within 5 s after the onset of the stimulus. The slope of this relationship was defined as baroreflex sensitivity. Baroreflex sensitivity averaged 7.3 +/- 0.8 ms/mmHg. The cycling tourists underwent an exercise test on a bicycle ergometer until exhaustion, and oxygen uptake, pulmonary ventilation, peak heart rate and exercise duration were determined. In single and multiple regression analysis, baroreflex sensitivity was not significantly related to basal heart rate, peak oxygen uptake and ventilation, duration of exercise or other training characteristics. The results suggest that in man the so-called sensitivity of the carotid baroreflex control of heart rate is not influenced by the level of physical fitness and therefore the measurement of these characteristics can be neglected in evaluating baroreflex sensitivity.

Adolescent↗
PubMed1985

Differential responses of plasma aldosterone, cortisol and adrenocorticotropin to two dopamine receptor antagonists.

The response of plasma aldosterone, cortisol and adrenocorticotropin (ACTH) to the dopamine antagonists metoclopramide and domperidone, administered intravenously in a dose of 1 mg/kg, was investigated in healthy volunteers. Within 15 min after metoclopramide administration, plasma aldosterone (+ 99%), cortisol (+ 75%) and ACTH (+ 55%) increased (p less than 0.001), whereas the plasma levels of these hormones were not altered after domperidone. The differential responses of plasma aldosterone and cortisol to high doses of metoclopramide and domperidone are therefore, at least partially, mediated via the enhanced adrenal stimulation by ACTH after metoclopramide.

Adrenocorticotropic Hormone↗
PubMed1984

Stimulation of tyrosine phosphorylation in lectin treated human lymphocytes.

Large increases in tyrosine phosphorylation have been detected in subcellular matrixes isolated from lectin treated human lymphocytes. In lectin stimulated cells proteins of molecular weight 105, 75, 58 and 35 kDa contained phosphotyrosine (P-tyr) whereas non-stimulated cells had no 105 and low levels of P-tyr in proteins of 75, 58 and 35 kDa. In stimulated cells increased tyrosine kinase activity was also shown using gastrin as substrate. In both stimulated and non-stimulated cells the 58 kDa phosphoprotein was the most heavily labelled, after partial proteolysis of the 58 kDa different phosphopeptides were generated. A peptide with a sequence analogous to the autophosphorylated tyrosine site of pp60src inhibited tyrosine phosphorylation in stimulated cells. The lymphocyte system provides a useful tool to study normal tyrosine protein kinases and their role in cellular proliferation.

Detergents↗
PubMed1984

Bradycardia, ventricular pauses, syncope, and sports.

16 athletic patients were examined because of syncope, Stokes-Adams attacks, or both. The life-threatening condition required pacemaker implantation in 7 patients. 8 of the 9 other subjects became symptom-free after stopping heavy physical training. 37 top-ranking athletes underwent 24 h Holter monitoring. Pauses longer than 2 s occurred in 19% and resulted from sinus arrest. The longest pause lasted 2.5 s. Second-degree atrioventricular block was noted in 13%.

Adams-Stokes Syndrome↗
PubMed1984

Systolic time intervals in coronary heart disease at rest and during exercise: effect of physical training with and without beta blockade.

Systolic time intervals (STIs) were measured in recumbency at rest and in the sitting position at rest and during exercise, before and after a physical training program, in 28 patients with coronary heart disease. Fifteen patients were treated with a beta-blocking drug and 13 were not. After training, oxygen uptake at peak exercise increased similarly in both groups, by 41% and 37%, respectively, whereas heart rate at rest and during submaximal exercise decreased in both groups. Left ventricular (LV) ejection time (ET) adjusted for heart rate was not significantly affected by training. The rate-corrected preejection period (PEP) and the PEP/LVET ratio decreased after training. The changes in the STI after training were not related to the level of physical activity during testing and were similar in the patients treated with beta-blocking drugs and in those not so treated. The changes after training in STI at rest and at exercise in both treatment groups suggest that LV function improves during the training period and that beta-blockade does not alter this outcome.

Adrenergic beta-Antagonists↗
PubMed1984

Identification of a 58,000 daltons phosphoprotein with tyrosine protein kinase activity in a murine lymphoma cell line.

A very high level of tyrosine protein kinase (TPK) activity has been recently detected in a murine lymphoma, induced by Moloney murine leukemia virus. A major endogenous substrate for tyrosine phosphorylation in vitro is a protein of Mr 55-60,000 (p58) associated with the detergent insoluble matrix of LSTRA cells; in the present work p58 was solubilized, isolated by anion exchange chromatography and then precipitated by antiphosphotyrosine antibodies. Through these steps of isolation, TPK activity was measured by the use of a simplified gastrin phosphorylation assay. It is demonstrated that the TPK activity copurifies with p58, which leads to the conclusion that p58 bears itself the enzymatic activity. Although functionally similar to other enzymes of this group, this newly characterized TPK does not seem to be closely related to one of the previously documented TPK. This suggests either that this protein is the product of a so far unrecognized cellular TPK gene or that it derives from a rearrangement of one of the previously described TPK genes.

Animals↗
PubMed1984

Control of protein synthesis in human reticulocytes by heme-regulated and double-stranded RNA dependent eIF-2 alpha kinases.

Heme-deficiency and double-stranded RNA (dsRNA) activate distinct cyclic 3':5'-AMP independent protein kinases (HRI and dsI, respectively) in rabbit reticulocyte lysates. These kinases inhibit protein synthesis by phosphorylating the 38,000 daltons (38K) subunit of the initiation factor eIF-2 (eIF-2 alpha). Using separation techniques to obtain a reticulocyte enriched fraction and reticulocyte-free erythrocytes, we have prepared lysates of these fractions from normal human whole blood. Human reticulocyte-enriched lysates contain the hemin-regulated and dsRNA-dependent protein kinases which inhibit protein synthesis and which phosphorylate rabbit eIF-2 alpha. An endogenous 38K polypeptide which co-migrates with rabbit eIF-2 alpha is also phosphorylated. In contrast, human mature erythrocytes contain little or no heme-regulated or dsRNA-dependent eIF-2 alpha kinase activities which are inhibitory of protein synthesis.

Blood Proteins↗
PubMed1984

Effect of prenalterol on orthostatic hypotension in the Shy-Drager syndrome.

Treatment of idiopathic orthostatic hypotension is often unsatisfactory. A patient with the Shy-Drager syndrome, in which the most important symptom is orthostatic hypotension, was treated with prenalterol, initially 30 mg six times daily. The dosage was reduced to 30 mg four times daily because of the development of complex ventricular premature beats. Orthostatic symptoms were reduced and standing blood pressure increased. Fludrocortisone 0.5 mg a day was added to treatment with further improvement. This clinical effect was maintained throughout 12 months of follow up, during which the treatment was continued unchanged. Prenalterol was effective in reducing orthostatic symptoms in this patient. Further studies in patients with a similar haemodynamic pattern are indicated.

Adrenergic beta-Agonists↗
PubMed1984

Influence of physical training on blood pressure, plasma renin, angiotensin and catecholamines in patients with ischaemic heart disease.

Eighteen patients with ischaemic heart disease were trained for 3 months, three times a week. The effectiveness of the training programme was demonstrated by increases of 27% in peak oxygen uptake and 29% in exercise duration, and by a decrease in resting and submaximal heart rates. Blood pressure, however, was not significantly affected during the training period. At rest and at submaximal exercise plasma renin activity (PRA) was lower after training. Plasma angiotensin I concentration (PA I) and angiotensin II concentration (PA II) were not significantly affected. Plasma aldosterone concentration (PAC), only measured at rest, was not significantly changed after the training period, while plasma norepinephrine (PNE) and epinephrine (PE) concentrations were significantly decreased, but only at high levels of exercise. A reduced sympathetic tone after training, suggested by the lower heart rates and the tendency to a decrease in PNE, is a likely explanation for the decrease in PRA. However, despite this decrease, PA I, PA II, and PAC were not significantly changed after training; the reason for this disrepancy is unknown.

Angiotensins↗