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Biomedical subjects

E Moerman

Publications and source records attributed to E Moerman.

At least 19 recordsLinked to original sources
PubMed1992

The influence of aging on the stereoselective pharmacokinetics of propranolol in the rat.

The influence of aging on the pharmacokinetics and the tissue distribution of (R)- and of (S)-propranolol was studied in 3-, 12-, and 24-month-old rats. After both iv and oral administration of rac-propranolol, the plasma concentrations were higher for the (R)- than for the (S)-enantiomer. For the tissue concentrations, the reverse was true. The free fraction of (S)-propranolol in plasma was about 4 times larger than that of (R)-propranolol, and this is the main factor responsible for the differences in kinetics between the two enantiomers. There was a suggestion for a difference in tissue binding between the two enantiomers. With aging, the plasma and tissue concentrations of both enantiomers increase, probably due to a decrease in blood clearance. Tissue binding did not change much with aging. Notwithstanding the marked differences between the kinetics of the propranolol enantiomers, the changes which occur with aging affect both enantiomers to the same degree.

Administration, Oral↗
PubMed1992

Influence of lansoprazole treatment on diazepam plasma concentrations.

The possible influence of long-term treatment with lansoprazole on the single-dose pharmacokinetics of diazepam was investigated in 12 healthy male volunteers. In this double-blind randomized crossover study, 60 mg lansoprazole or placebo was administered once daily for 10 days. One hour after administration on day 7, 0.1 mg/kg diazepam was administered intravenously, and blood was collected up to 96 hours after the injection for plasma diazepam and desmethyldiazepam measurement. During the placebo session, the plasma elimination half-life, clearance, and volume of distribution of diazepam were 26.0 +/- 1.6 hours, 22.5 +/- 1.1 ml/hr/kg, and 0.82 +/- 0.04 L/kg, respectively. These parameters were not significantly different during the lansoprazole session. The mean plasma concentrations of desmethyldiazepam were similar in both sessions. These findings illustrate that long-term treatment with a therapeutic dose of lansoprazole does not interfere with the metabolism of diazepam.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1992

Urinary excretion of ephedrine after nasal application in healthy volunteers.

The urinary excretion of ephedrine after intranasal administration of the drug was studied in 8 healthy volunteers. Ephedrine (6 drops of a commercial 0.75% nasal ephedrine solution in each nasal cavity) was administered 4 times at intervals of 2 h (total amount applied equivalent to approximately 14 mg ephedrine), and urine was collected each hour for 10 h; the volunteers exercised on a bicycle ergometer at 50% of their VO2max for 2 h after the last ephedrine application. Ephedrine was detected in all urine samples. The urinary ephedrine concentration ranged from 0.9 to 16.5 micrograms mL-1; the number of urine samples with an ephedrine concentration exceeding 5 micrograms mL-1 ranged from 1/10 (volunteer 2) to 9/10 (volunteers 1 and 3). The mean percentage of dose recovered within 10 h was 33% (range 23-50%). There was a weak but significant negative correlation between urinary pH and amount of ephedrine in the urine; exercise did not consistently influence the urinary amount. These results illustrate the systemic availability of ephedrine upon intranasal administration and show that the therapeutic use of a nasal ephedrine formulation by an athlete on the day of a competition can lead to a urinary ephedrine concentration above 5 micrograms mL-1, which is considered positive in current doping regulations of the International Union of Cyclists.

Administration, Intranasal↗
PubMed1990

Catecholamine levels and pacing behavior of QT-driven pacemakers during exercise.

It is thought that increasing catecholamine levels in the heart are partly responsible for shortening of the repolarization time and so indirectly for the pacing behavior of the QT driven pacemaker. Adrenaline and noradrenaline (NA) plasma levels were determined at rest, during symptom-limited exercise, and during recovery more than 1 month after the implantation of a 919 or a Rhythmyx pacemaker (Vitatron, The Netherlands) in eight patients (age 54-85 yrs). Significant increases were detected in NA level (from 0.57 +/- 0.23 ng/mL to 2.15 +/- 0.76 ng/mL), but not in the circulating adrenaline level. The correlation coefficient of the mean pacing rate and the mean NA level during exercise and recovery was 0.963 (P less than 0.0001), the correlation coefficient with the mean oxygen consumption was 0.888 (P less than 0.01). No correlation with the adrenaline level was observed. The correlation coefficient of the changes of pacing rate and the changes of NA level during exercise and recovery was 0.882 (P less than 0.005). The pacing rate of the new generation of QT driven pacemakers is closely correlated with the noradrenaline spillover in the plasma, not with the adrenaline level. A short delay (less than 1 minute) is observed in the adaptation.

Aged↗
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

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↗
PubMed1988

Effects of opioid antagonism on the haemodynamic and hormonal responses to exercise.

1. Physical effort involves, along with an increase in the plasma concentration of beta-endorphin, profound adaptations of the circulation and the endocrine system. The effects of opioid antagonism on the responses of blood pressure, heart rate and several hormones to exercise were therefore studied in 10 normal men. They 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). 2. Intra-arterial pressure and heart rate were continuously monitored, but were not affected by naloxone. 3. At rest, opioid antagonism produced a rise in plasma renin activity and in plasma adrenocorticotropin, cortisol and aldosterone, but only the stimulation of the two adrenocortical hormones differed significantly from the control experiments; at rest naloxone also prevented the fall in plasma adrenaline, which occurred with saline infusion. Furthermore, the exercise-induced rises in plasma angiotensin II, aldosterone, cortisol, noradrenaline and adrenaline were higher on naloxone than on saline, while a similar tendency was also present for the increases with exercise in plasma renin activity and plasma adrenocorticotropin. Neither at rest nor during exercise did opioid antagonism alter plasma lactate and glucose and serum insulin and growth hormone. 4. In conclusion, (1) endogenous opioids are not involved in the responses of blood pressure and heart rate to supine exercise; (2) at rest and during exercise, the endogenous opioids inhibit the secretion of adrenocorticotropin, aldosterone, cortisol, noradrenaline and adrenaline; (3) they also inhibit the plasma renin-angiotensin II system indirectly via the catecholamines.

Adrenal Cortex Hormones↗
PubMed1988

Effects of physical endurance training on the plasma renin-angiotensin-aldosterone system in normal man.

The effect of physical endurance training on the plasma renin-angiotensin-aldosterone system was studied in 27 normal sedentary volunteers aged between 20 and 55 years, using a randomized two-period cross-over study design. After 4 months of training (2.5 h/week), peak oxygen uptake and physical working capacity at a heart rate of 130 beats/min were increased by 16% (P less than 0.01) and 29% (P less than 0.001) respectively, whereas resting heart rate was decreased by 15% (P less than 0.001). The plasma noradrenaline concentration and haematocrit were both decreased (P less than 0.01) after training. For the total group of subjects, the small decreases in plasma renin activity (PRA) and in the plasma concentrations of angiotensin-I, angiotensin-II and aldosterone were not statistically significant. However, the change in PRA during the training period was negatively correlated with the increase in physical working capacity (r = -0.49, P less than 0.01), suggesting that PRA decreased only in those subjects with the greatest increase in exercise capacity. Also, the change in plasma aldosterone during training was negatively related to the rise in physical working capacity (r = -0.57, P less than 0.01). Furthermore, the changes in plasma angiotensin-I (r = 0.75), angiotensin-II (r = 0.49) and aldosterone (r = 0.43) during the training period correlated positively with the change in PRA. It is concluded that physical endurance training, leading to a substantial gain of physical working capacity, suppresses the plasma renin-angiotensin-aldosterone system in normal man.

Adult↗
PubMed1987

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↗
PubMed1987

Effects of felodipine and metoprolol on blood pressure, plasma renin, angiotensin II, aldosterone and catecholamines in hypertensive patients.

Oral administration of felodipine to 10 patients with mild essential hypertension acutely reduced the brachial artery pressure by 15/13mm Hg. The tachycardia which occurred was sustained for 90 minutes together with an elevated plasma noradrenaline concentration. Addition of intravascular metoprolol after 90 minutes decreased heart rate. The felodipine-induced increase of plasma renin activity (100%; p less than 0.001) was completely reversed by metoprolol. Plasma angiotensin II (PA II) rose by 15% (p less than 0.05) during felodipine, whereas plasma aldosterone concentration was not significantly affected.

Adult↗
PubMed1987

Effects of felodipine on blood pressure and humoral factors in sodium-replete humans at rest and during exercise.

The effect of short-term calcium antagonism with felodipine on blood pressure and on plasma catecholamines, renin, and aldosterone was studied in 10 normal volunteers at rest and during incremental bicycle exercise. At rest, diastolic blood pressure was slightly increased during felodipine treatment, whereas systolic pressure and heart rate were not significantly changed. The plasma noradrenaline concentration and plasma renin activity were increased during felodipine treatment; the plasma adrenaline and aldosterone concentrations, on the contrary, were not significantly changed. The rises in plasma renin activity, plasma aldosterone, and plasma adrenaline and noradrenaline concentrations produced by exercise were not significantly affected by felodipine. It is concluded that the rise in plasma renin activity during calcium antagonism with felodipine is not accompanied by a significant increase in plasma aldosterone. Furthermore, the present data suggest that, at least during exercise, calcium antagonism does not interfere with the mechanisms underlying the exercise-induced activation of renin and aldosterone release.

Adult↗
PubMed1987

Effects of calcium antagonism on the resting and exercise-stimulated renin-aldosterone axis.

The effect of short-term calcium antagonism with felodipine on blood pressure and on some biochemical plasma variables such as catecholamines, renin and aldosterone was studied in 10 normal volunteers at rest and during incremental bicycle exercise. At rest, diastolic blood pressure was slightly decreased during felodipine, whereas systolic pressure and heart rate were not significantly changed. The plasma noradrenaline concentration and plasma renin activity were increased during felodipine treatment; the plasma adrenaline and aldosterone concentrations on the contrary, were not significantly changed. The rises in plasma renin activity, plasma aldosterone and plasma adrenaline and noradrenaline concentrations produced by exercise were not significantly affected by felodipine. The plasma calcium concentration was significantly higher during felodipine treatment than during placebo and this was accompanied by an increased urinary calcium excretion. It is concluded that the rise in plasma renin activity during calcium antagonism with felodipine is not accompanied by a significant increase in plasma aldosterone. Furthermore, the present data suggest that, at least during exercise, calcium antagonism does not interfere with the mechanisms underlying the exercise-induced activation of renin and aldosterone release.

Aldosterone↗
PubMed1986

Differentiation of exercise-induced metabolic responses during selective beta 1- and beta 2-antagonism.

The effect of beta 1- or beta 2-antagonism on the plasma levels of glucose, lactate, triglycerides, and free fatty acids was studied in seventeen normal male volunteers. All subjects performed three graded and uninterrupted exercise tests until exhaustion. Prior to each exercise test they received in a randomized order during three consecutive days either placebo or a predominant beta 1-blocker (atenolol, 50 mg once per day) or a predominant beta 2-blocker (ICI 118,551, 20 mg t.i.d.), according to a double-blind cross-over study design. Atenolol increased the plasma level of glucose at rest but did not influence the rise in plasma glucose during exercise. ICI 118,551 did not change the resting plasma glucose level, but it prevented the exercise-induced rise in plasma glucose, observed during placebo. During beta 1-antagonism the plasma lactate concentration at rest and during or after exercise was not different from placebo. During beta 2-blockade the exercise-induced rise in plasma lactate tended to be suppressed, and during recovery the plasma lactate levels were significantly lower than during placebo. The serum triglycerides concentration at rest and exercise was not altered, either by beta 1- or by beta 2-antagonism. Atenolol and ICI 118,551 did not affect the serum level of free fatty acids at rest, but at moderate exercise the serum free fatty acids concentration was lower during beta 1-blockade than during placebo. Our results provide further evidence that beta 2-adrenergic receptors are involved in the regulation of the plasma levels of glucose and lactate during exercise.

Adult↗
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↗
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↗
PubMed1984

Responses of the systemic circulation and of the renin-angiotensin-aldosterone system to ketanserin at rest and exercise in normal man.

The systemic circulation at rest and during exercise was studied in ten normal male volunteers, after placebo on one occasion and after acute intravenous administration of the serotonergic antagonist ketanserin on another occasion. The effects of ketanserin on the components of the renin-angiotensin-aldosterone system, on plasma catecholamines and on exercise capacity for graded uninterrupted exercise were also investigated. At rest in recumbency rapid intravenous injection of 10 mg of ketanserin, followed by a continuous infusion of 2 mg/h, produced an acute but transient fall in mean intra-arterial pressure of 6 mmHg compared with placebo. After 15 min the mean arterial pressure with ketanserin was within 2 mmHg of the mean pressure with placebo. In the sitting position both at rest and up to 30% of maximal work rate, the mean arterial pressure during ketanserin did not differ from the pressure on placebo. However, at higher levels of physical activity the rise in mean arterial pressure was lower with ketanserin; the pressure achieved with placebo was 7.5 mmHg higher at maximal work rate. Heart rate and cardiac output were significantly higher during ketanserin. When the subjects were lying down and resting, plasma noradrenaline and adrenaline levels, plasma renin activity and angiotensin II concentration were not affected by ketanserin; however, these values were higher in the sitting position both at rest and during exercise. Plasma aldosterone was reduced by ketanserin during exercise and also when the subject was resting in the recumbent position.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Haemodynamic and humoral responses 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 six weeks. Resting intra-arterial 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 haemodynamic 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. Mean pulmonary arterial pressure and capillary wedge pressure were not significantly affected, but pulmonary vascular resistance decreased by 15%. The pressor response to methoxamine was significantly reduced by ketanserin. Both plasma noradrenaline and adrenaline concentrations increased, plasma renin activity and angiotensin II concentration decreased, and plasma aldosterone concentration was unchanged. The data indicate that ketanserin induces arteriolar dilatation, possibly related to an alpha-1-antagonistic action and to a reduced circulating angiotensin II concentration. The haemodynamic response is complex, and an increase in cardiac output limits the hypotensive effect. There is no firm evidence of an effect on venous tone as cardiac filling pressures do not change.

Adult↗