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Biomedical subjects

J L Imbs

Publications and source records attributed to J L Imbs.

At least 19 recordsLinked to original sources
PubMed1992

Effects of chlorpromazine and lorazepam on explicit memory, repetition priming and cognitive skill learning in healthy volunteers.

To assess the influence of neuroleptics on explicit memory and two forms of implicit memory, repetition priming and cognitive skill learning, the effects of two low doses of chlorpromazine (12.5 and 25 mg orally) were contrasted to those of lorazepam (2.5 mg orally) and of a placebo using a free-recall task, a word-completion task and repeated testing on the Tower of Toronto puzzle, a version of the Tower of Hanoi puzzle. Seventy-two healthy volunteers took part in this double-blind study. Chlorpromazine spared free-recall and word-completion performance, but impaired the acquisition of a cognitive routine in the subjects who completed the first trials of the Tower of Toronto puzzle efficiently. Lorazepam induced an opposite pattern of memory disruption. These preliminary results suggest that chlorpromazine and lorazepam induced a double dissociation between priming and the acquisition of a cognitive routine. They provide evidence that the two forms of implicit memory rely upon distinct neurochemical systems, the latter, but not the former, being dependent upon dopaminergic systems.

Adult↗
PubMed1992

Differential effects of diazepam and lorazepam on repetition priming in healthy volunteers.

The effects of two benzodiazepines, diazepam (15 or 20 mg orally) and lorazepam (1.75 or 2.5 mg orally), and a placebo on explicit memory, lexical priming and perceptual priming were assessed using a free-recall, a word-completion and a picture-completion test. The picture-completion test included two different study conditions intended to manipulate the magnitude of the priming effect. Sixty healthy volunteers took part in this double-blind study. Free-recall performances were altered by both drugs. Lorazepam impaired word-completion and picture-completion performance, whereas diazepam only exhibited a deleterious effect on the more sensitive of the two measures of the picture-completion test. These results indicate that the two benzodiazepines have differential amnestic effects. It is suggested that these differential effects could be accounted for by a different cortical distribution of the two benzodiazepines.

Adult↗
PubMed1992

In vitro stability of the inhibition of serum converting enzyme by fosinopril.

With captopril, it has been shown that an erroneous measurement of serum angiotensin converting enzyme (ACE) can be induced by the dissociation of the inhibitor-ACE complex during long-term storage. We have studied the possible dissociation of the fosinopril-ACE complex during the storage of serum samples from healthy male volunteers given a single dose of fosinopril. Serum samples were collected from 5 volunteers, 5 min before, then 4 and 24 h after a unique oral dose of 10 mg fosinopril. ACE activity was measured by a colorimetric and a fluorimetric assay during the hour following the sampling (day 0) and after 21 or 61 days of storage at -20 or -196 degrees C. The degree of ACE inhibition measured in vitro in fresh serum samples differed according to the technique used. Fosinopril has a long-lasting effect with 80% inhibition 24 hours after drug administration. Storage at -20 and -196 degrees C induced a significant decrease in the degree of inhibition measured with the colorimetric method. With the fluorimetric method, a decrease in ACE inhibition was only observed after storage at -20 degrees C but not at -196 degrees C.

Administration, Oral↗
PubMed1991

[Hypertrophic cardiomyopathy with left ventricular dynamic obstruction syndrome in hypertensive adult patients].

Seven adult patients with old and severe arterial hypertension were found to have hypertrophic cardiomyopathy with left ventricular obstruction demonstrated by an isoproterenol test. Whenever feasible, confirmation that systolic obstruction of the left ventricular outflow tract was due to anterior systolic movement of the mitral valve was obtained. Echocardiography revealed a number of ultrasonic features (asymmetrical septal hypertrophy, small left ventricle and clear-cut reduction of the left ventricular outflow tract) which put these cases closer to the primary hypertrophic cardiopathy group than to the hypertensive cardiomyopathy group, with a similar history of hypertension. Detecting this group is facilitated by the use of vasoactive drugs in patients with these echocardiographic features. This is important since there is a risk of poor tolerance to vasodilators, notably nitrates, which may suddenly reveal the left ventricular dynamic obstruction syndrome. These patients are also exposed to paroxysmal atrial fibrillation.

Adult↗
PubMed1991

The effects of muzolimine and urine from muzolimine-treated rats on Na+K+Cl- cotransport in Madin-Darby canine kidney cells.

Muzolimine is a loop diuretic with an original chemical structure devoid of the acidic or sulfonamide group known to be necessary for an interaction with Na+K+Cl- cotransport. We studied the effects of urine from muzolimine-treated rats on the Na+K+Cl- cotransport-dependent 86Rb influx in MDCK cells. Na+K+Cl- cotransport was inhibited by urine obtained 15 min (42% inhibition) and 60 min (49% inhibition) after muzolimine injection (50 mumol/kg i.v.). Muzolimine itself was not detectable in the urine. Probenecid (100 mumol/kg i.v.) suppressed both the diuretic effect of muzolimine and the inhibition of Na+K+Cl- cotransport by urine from muzolimine-treated rats. These results suggest that the diuretic effect of muzolimine is due to the metabolism of muzolimine into an active compound which inhibits Na+K+Cl- cotransport after its secretion into the tubular lumen via a proximal pathway. The direct effect of muzolimine on Na+K+Cl- cotransport in MDCK cells was also tested: surprisingly, the inhibition of 86Rb influx was significant in the presence of muzolimine (IC50 = 1.44 microM). We show that this effect was due to the metabolism of muzolimine by these cells into an active compound.

Animals↗
PubMed1991

[3H]ramiprilat binding to the angiotensin-converting enzyme in rat renal brush-border membranes: the effect of chloride.

The [3H]ramiprilat binding to the angiotensin-converting enzyme (ACE) in rat renal brush-border membranes was studied. At pH 7.9, and in the presence of 50 mM NaCl, specific binding of [3H]ramiprilat was saturable with a dissociation constant KD = 5.05 nM and maximum number of binding sites of 1.52 pmol/mg prot. [3H]Ramiprilat binding was completely inhibited by specific inhibitors of ACE: ramiprilat, ramipril, enalaprilat, enalapril and captopril. [3H]Ramiprilat binding was Zn2(+)- and Cl(-)-dependent. In the presence of EGTA, which chelates Zn2+ ions, ramiprilat binding was inhibited, but the addition of Zn2+ restored the initial binding. Binding was maximum in the presence of 10 mM NaCl while higher NaCl concentrations decreased the binding, corresponding to a decrease in affinity. The association and dissociation kinetics were also NaCl-dependent. In the absence of NaCl, association and dissociation kinetics were rapid and monophasic. Two-step dissociation kinetics appeared in the presence of 10, 50 and 300 mM NaCl and dissociation time increased with the NaCl concentration. These results confirmed the role of Cl- in the isomerisation and the stability of the membrane-associated ACE-inhibitor complex.

Alkaline Phosphatase↗
PubMed1991

Effects of dopamine prodrugs and fenoldopam on glomerular hyperfiltration in streptozotocin-induced diabetes in rats.

The effects of dopamine (DA) prodrugs (L-dopa and gludopa) and of a D1-selective agonist (fenoldopam) on glomerular hyperfiltration were studied in the early stage of diabetes in rats. Wistar rats received one injection of streptozotocin (STZ) and were treated 1 week later with L-dopa (2 x 10 mg/kg/day, s.c.), gludopa (2 x 3 or 2 x 10 mg/kg/day, s.c.), or fenoldopam (2 x 0.3 or 2 x 1 mg/kg/day, s.c.). Their renal functions were compared with those of untreated diabetic and nondiabetic control rats. STZ injection led to hyperglycemia that was kept moderate (20-25 mmol/L) by daily insulin therapy (2-4 U of NPH insulin). Within 2 weeks, glomerular hyperfiltration (polyfructosan clearance) developed in diabetic rats (30% increase vs. nondiabetic control). A rise in renal plasma flow (PAH clearance) was sometimes observed. One week of treatment with either L-dopa, gludopa, or fenoldopam normalized the glomerular filtration rate and decreased filtration fraction. These corrections occurred despite similar metabolic disturbance and kidney hypertrophy. Gludopa was less well tolerated by diabetic rats than L-dopa. Results with L-dopa showed that the normalization of glomerular hyperfiltration was linked to DA synthesis and stimulation of D1 receptors, since it was reversed by carbidopa, a dopa decarboxylase inhibitor, and by SCH 23390, a D1-selective antagonist. These data show that DA prodrugs and a D1 agonist can suppress diabetic glomerular hyperfiltration in the very early course of the disease in rats.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

In vitro tissue potencies of converting enzyme inhibitors. Prodrug activation by kidney esterase.

The inhibition of angiotensin converting enzyme by ramipril, ramiprilat, enalapril, enalaprilat, and captopril was studied in the plasma and various tissues (lung, heart, renal cortex, renal medulla) of normotensive rats and spontaneously hypertensive rats. Displacement curves for [3H]ramiprilat were established on each tissue with the converting enzyme inhibitors, and their potencies were expressed as the concentration that inhibited 50% of the specific [3H]ramiprilat binding. In the plasma, lung, and heart, the order of activities was: ramiprilat greater than enalaprilat greater than captopril greater than ramipril greater than enalapril. This order was different in the kidney (cortex and medulla): ramiprilat greater than enalaprilat greater than ramipril greater than captopril greater than enalapril. For ramiprilat, enalaprilat, and captopril, there were no differences in their respective potencies between tissues or between rat strains. However, the two prodrugs ramipril and enalapril were 10-30 times more active in the kidney than in the other tissues in both groups of rats. This was due to the deesterification of the prodrugs: in the presence of an esterase inhibitor (diethyl nitrophenyl phosphate, 10 microM), the potencies of ramipril in the kidney were not different from that obtained in the lung, which was not affected by the presence of the esterase inhibitor. These results suggest that the variations in the tissue activities of an angiotensin converting enzyme inhibitor are probably not due to differences in tissue affinities of the angiotensin converting enzyme inhibitor but depend on the concentration of this angiotensin converting enzyme inhibitor in each tissue.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

[Changing factors of the activity of angiotensin converting enzyme of renal brush border in rats].

In the kidney, angiotensin I-converting enzyme (ACE) is present in the vascular endothelial cells and in the brush border of epithelial cells of the proximal tubule. In spite of this well-known distribution of ACE, little is known of its regulation. In order to elucidate the possible mechanisms of control for brush border ACE, the effects of dexamethasone (DM), (40 micrograms s.c. per day, for 7 days) and triiodothyronine (T3) 0.5 mg/kg s.c. per day, for 10 days) were investigated in male Wistar rats. Plasma and brush border ACE activities were measured by fluorimetry in the presence of an artificial substrate Cbz-Phe-His-Leu and brush border ACE was characterized with a binding assay using 3H-ramiprilat, a specific radiolabelled ACE inhibitor. DM elicited a significant decrease in plasma ACE activity (from 0.46 +/- 0.03 to 0.28 +/- 0.02 nmol His-Leu/min/mg protein) but did not alter enzyme activity in the brush border: 47.12 +/- 5.12 nmol His-Leu/min/mg protein (control, n = 6) and 47.78 +/- 5.63 (DM, n = 6). Administering T3 produced a marked increase in the brush border ACE activity (from 42.87 +/- 4.9 to 81.41 +/- 11.7 nmol His-Leu/min/mg protein). Similarly, the maximum number of 3H-ramiprilat-binding sites increased in the brush border, indicating a good correlation between ACE activity and the quantity of 3H-ramiprilat bound. Thus, the variation in tissue ACE activity corresponded to a change in the enzyme concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

[Comparison of the efficacy and tolerability of sustained-release verapamil and captopril in mild to moderate essential arterial hypertension].

A randomised, double-blind, double-placebo trial compared the efficacy and safety/acceptability of sustained release verapamil and of captopril in two parallel groups of patients with mild to moderate hypertension. After a 2 week placebo period, 45 patients were randomised into 2 groups, the 1st group (n = 22) given sustained release verapamil (240 mg/24 h) as a single morning dose and the second (n = 23) captopril 25 (50 mg/24 h) as two daily divided doses. Treatment was given for 75 days, with the possibility of a combination of sustained release verapamil + captopril from day 45 onwards if diastolic blood pressure remained at 95 mmHg or more. After 45 days of treatment, the reduction in supine diastolic blood pressure did not differ significantly in the 2 groups (-10.4 mmHg in the sustained release verapamil group and -9.7 mmHg in the captopril), with 68.2 per cent responders to sustained release verapamil and 52.2 per cent in the captopril group. After 75 days of treatment, once again there was no significant difference in efficacy between the two groups: -14 mmHg for diastolic pressure and 80 per cent responders in patients treated with sustained release verapamil, -11.3 mmHg and 62.5 per cent responders in the captopril group. The percentage of responders was 58.3 per cent in the group treated with the combination of sustained release verapamil + captopril from day 45 onwards. The number of patients showing evidence of clinical or electrocardiographic adverse reactions was not significantly different: 20.7 per cent in the sustained release verapamil group and 34.8 per cent in the captopril group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

[Do renal vascular D2 receptors exist?].

Two dopamine receptors are present on the renal vasculature: post-synaptic D1-receptors and neuronal D2-receptors. The existence of postsynaptic vascular D2-receptors is now under discussion. The aim of this study was to characterize in vitro the renal vascular response to bromocriptine, a D2 preferential agonist. Bromocriptine (10(-7) to 3.10(-5) M) induced a concentration dependent relaxation (EC50 = 1.4 +/- 0.1 x 10(-6) M, m +/- SEM, n = 5) on the isolated perfused rat kidney whose vascular tone had been previously increased by 25% with prostaglandin F2 alpha and adrenoceptors blocked (phenoxybenzamine 10(-5) M, sotalol 10(-5) M). Response to bromocriptine was comparable to that induced by dopamine on terms of EC50 and Emax (87 +/- 3% reversion of the increase in renal vascular resistance induced by prostaglandin F2 alpha). Nevertheless, unlike response to dopamine, bromocriptine-induced relaxation was not antagonized by the selective D1-receptor antagonist, SCH 23390 (3 x 10(-9) M) but was inhibited by selective D2-receptor antagonists, domperidone (10(-8) M) and DO 710 (3 x 10(-8) M). To account for renal vasodilatation, an interaction of bromocriptine with 5-HT receptors was excluded. Indeed, neither 8-OHDPAT, 5-methoxytryptamine nor 5-HT were able to induce any renal vasodilatation on the isolated perfused rat kidney and domperidone is devoid of antagonist activity on 5-HT receptors. The present results suggest that bromocriptine-induced vasodilatation on the rat renal vascular bed was linked to an interaction with vascular postsynaptic D2-receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

[Role of sleep apnea in essential arterial hypertension].

Because sleep apnoea syndrome is often associated with arterial hypertension, it has been suggested that sleep apnoea might be responsible for hypertension. This hypothesis is mainly based on epidemiological studies showing a statistically significant association between snoring and arterial hypertension; this association remains true even after data correction to take into account the increased frequency of snoring with age and overweight. However, this statistical link is no evidence of a cause-effect relationship, and the mechanism through which sleep apnoea syndrome could produce arterial hypertension remains unknown. Yet treatment of sleep apnoea syndrome seems to improve arterial hypertension, and this alone would justify a search for sleep apnoea syndrome in all patients presenting with arterial hypertension.

Atrial Natriuretic Factor↗
PubMed1990

[Management of hypertensive patients in private practice].

In private practice mild or moderate arterial hypertension is controlled primarily to prevent the development of a severe, organ-damaging hypertensive disease. The general practitioner's approach to management proceeds in 3 steps. 1) He must decide to initiate a treatment after obtaining sufficient evidence that the hypertension is permanent and after starting to correct the associated risk factors. 2) He must select a single-drug initial treatment among the four families of antihypertensive medications, viz.: diuretics, beta-blockers, angiotensin-converting enzyme inhibitors and calcium antagonists. The selection is based on the information available concerning the benefit/risk ratio of the preferred drug, its interactions with the pathologies that are often associated with hypertension, and its acceptability. Finding for each patient the optimal dosage with maximum effectiveness and minimum undesirable side-effects is of prime importance. 3) If this initial treatment fails, the practitioner must first make sure that his prescription was optimal in dosage and compliance. If this was the case, he must make a choice between another single-drug therapy and a combination therapy, using by preference two synergistic drugs in low doses.

Antihypertensive Agents↗
PubMed1990

Effects of scopolamine, trimipramine and diazepam on explicit memory and repetition priming in healthy volunteers.

The effects of scopolamine, an anticholinergic drug, of trimipramine, a tricyclic antidepressant with both anticholinergic and sedative properties, of diazepam and a placebo, on explicit memory and repetition priming were assessed using a free-recall task and a word-stem completion task. Forty-eight healthy volunteers took part in this double-blind study. Diazepam provoked a dissociation between free recall, which was profoundly impaired, and word completion, which was spared. No significant changes in memory performances were observed in the scopolamine group; however, a significant correlation between explicit and implicit memory performances was observed in this group. At the low dose used, the effects of trimipramine on memory were mild. The results suggest that the cholinergic system is involved in the priming effect.

Adult↗
PubMed1990

Metabolism and vascular effects of gamma-L-glutamyl-L-dopa on the isolated rat kidney.

Gamma-L-glutamyl-L-dopa (or gludopa), a dopamine (DA) prodrug, is selectively metabolized in vivo by the kidney through the sequential action of two renal enzymes, gamma-glutamyl transpeptidase (gamma-GT) and aromatic L-amino acid decarboxylase (AADC). This study was designed to analyze, in vitro, the factors regulating gludopa metabolism and its renal vascular effects. Rat kidneys were perfused in closed circuit with a cell-free perfusion buffer containing 6% bovine serum albumin (BSA). Adding gludopa (final concentration 10(-5) M in the perfusate) led to the release of DA both into urine and perfusate (0.53 +/- 0.21 and 1.38 +/- 0.28 nmol/min/g kidney wt, respectively, during the first 5 min after substrate addition, N = 5, mean +/- SEM). Total DA release (urine plus perfusate) was 73.7 +/- 15.8 nmol/g kidney wt within 30 minutes of recirculation. In non-filtering kidneys, total DA release in the recirculating medium was lower (12.5 +/- 1.4 nmol/g kidney wt, P less than 0.01). Glomerular filtration and access to the gamma-GT on the brush border membrane of proximal tubular cells are therefore required for the maximal conversion rate of gludopa. On filtering kidneys, L-dopa was also converted to DA, but at a higher rate than gludopa (total DA formed within 30 min of recirculation = 131.2 +/- 31.9 nmol/g kidney wt) and this rate was not reduced in non-filtering kidneys (224.2 +/- 41.7 nmol/g kidney wt DA formed within 30 min). Metabolic conversion of L-dopa by AADC is thus preserved in the case of an approach via the basolateral side of the proximal tubular cells. The renal vascular effects of gludopa were studied after vascular tone had been restored by continuous perfusion of PGF2 alpha and after the inhibition of alpha- and beta-adrenoceptors. Gludopa (3.10(-6) to 4.10(-5) M) elicited concentration-dependent renal vasodilatation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Renal dopamine synthesis from precursors.

In the Wistar rat in vivo L-dopa (10 mg/kg, subcutaneously) was shown to have the characteristics of a kidney-directed dopamine (DA) prodrug: two daily injections increased 24 h urinary DA excretion 450-fold but had no systemic effects on blood pressure and heart rate. In inactin-anesthesized rats, L-dopa increased natriuresis, diuresis and renal blood flow; these effects were linked to endorenal DA synthesis and to DA-1 receptor stimulation since they were suppressed by both carbidopa and SCH 23390. In the isolated perfused rat kidney, DA was synthesized from L-dopa with a greater yield than from gludopa. In nonfiltering kidneys, L-dopa metabolism was not limited when the access to dopa decarboxylase was restricted to the basolateral membrane. The same was not true for gludopa, for which the basolateral metabolism was low.

Animals↗