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Biomedical subjects

J L Imbs

Publications and source records attributed to J L Imbs.

At least 109 records · Page 6Linked to original sources
PubMed1989

Urinary excretion of guanosine 3':5'-cyclic monophosphate during sleep in obstructive sleep apnoea patients with and without nasal continuous positive airway pressure treatment.

1. It has recently been shown that obstructive sleep apnoea (OSA) patients have increased urinary water and salt excretion during sleep which tends to normalize with nasal continuous positive airway pressure (CPAP) treatment. 2. To investigate the mechanisms of these changes in renal function, nocturnal urinary excretion of catecholamines and guanosine 3':5'-cyclic monophosphate (cyclic GMP), which reflects atrial natriuretic factor (ANF) release, and next-morning plasma active renin concentrations were studied in 21 OSA patients on 2 consecutive nights, either untreated or treated with nasal CPAP. 3. In keeping with previous results, fractional urine flow and fractional Na+ and Cl- excretions were higher during untreated than during CPAP-treated nights. 4. No difference in plasma active renin concentration or in urinary excretion of noradrenaline, adrenaline, free dopamine and total dopamine could be demonstrated, but cyclic GMP excretion was significantly higher during untreated than during CPAP-treated nights. 5. The data are consistent with the hypothesis that the increased water and salt excretion in OSA patients is due to increased ANF release. 6. The proposed mechanism is an atrial distension due to increased (more negative) intrathoracic pressures during ineffective inspiratory efforts against the occluded upper airways which have been found in OSA.

Adult↗
PubMed1989

Renal effects of perindoprilat, an angiotensin-converting enzyme inhibitor, in the anesthetized dog.

The effects of perindoprilat on renal hemodynamics and the elimination of water and electrolytes were studied acutely in the anesthetized dog. Two groups of animals were compared, one on normal sodium and water, the other on an acutely restricted sodium and water diet. In all cases, perindoprilat injected into renal artery (0.1 and 0.5 mg/kg) reduced blood pressure. In the animals on a low sodium diet, perindoprilat increased renal blood flow from 2.2 +/- 0.3 to 2.9 +/- 0.3 ml/min/g and decreased the filtration fraction; the decrease in renal vascular resistance predominated on the efferent arteriole of the glomerule (45% decrease), preferential site for the vasoconstrictor action of angiotensin II. In the animals on a normal sodium diet, renal blood flow was also increased from 4.1 +/- 0.6 to 5.1 +/- 0.6 ml/min/g but without the filtration fraction being affected. The renal vascular resistance was decreased at both pre- and post-glomerular levels (respectively, 50 and 25% decrease). After sodium and water restriction, but not in animals on a normal sodium diet, perindoprilat increased the fractional elimination of water and electrolytes. This salidiuresis might be accounted for by the hemodynamic effect of converting enzyme inhibitor and the decrease it elicits in filtration fraction, modifying sodium and water reabsorption in the proximal tubule.

Anesthesia↗
PubMed1989

Assay of tissue angiotensin converting enzyme.

The distinction between a circulating renin-angiotensin system and a tissue renin-angiotensin system led us to determine tissue angiotensin converting enzyme (ACE) activity. This study establishes the experimental conditions for a good reproducibility of the fluorimetric assay of ACE and describes the use of [3H]ramiprilat to characterize ACE. Angiotensin converting enzyme activity was determined in rat lung, heart, aorta, and kidney (cortex and medulla) and in rabbit kidney (cortex, medulla, tubules, and glomeruli). ACE activity and [3H]ramiprilat binding does not increase in a linear fashion with the protein content of tissue extracts. Linearity limits varied from 1.0 to 2.0 mg of protein/ml (fluorimetry) and from 0.4 to 1.0 mg of protein/ml [( 3H]ramiprilat binding). Comparing ACE activity, measured by fluorimetry, with the amount of [3H]ramiprilat bound shows that the two techniques yield similar results.

Animals↗
PubMed1989

[Antihypertensive effect of perindopril. Experimental pharmacology].

This review of the pharmacological effects of perindopril is based on data from the literature and divided into three parts: (i) demonstration of the antihypertensive effect of the drug; (ii) characterization of its inhibitory effect on the angiotensin-converting enzyme, (iii) understanding of its mechanisms of action. The antihypertensive effect of perindopril has been demonstrated in spontaneously hypertensive rats or in artificially induced renovascular hypertension (1 clip-2 kidney, 1 clip-1 kidney). The intensity and duration of this effect is dose-dependent and is increased by stimulation of the renin-angiotensin system (renovascular hypertension, sodium depletion). The peripheral vascular resistance is decreased without corresponding increase in heart rate. The drug-induced vasodilatation predominates in the kidney bed and is associated, in dogs on low water and salt diet, with a rise in natriuresis. These effects are accompanied by inhibition of the angiotensin-converting enzyme. In vitro peridoprilate (the main active diacid of perindopril) is a potent (Cl50: 1.5 to 3.2 nM) competitive and relatively specific inhibitor of the angiotensin-converting enzyme. In vitro, perindopril competitively inhibits the pressive response to angiotensin I. In rats given an oral dose of 1 mg.kg-1 the activity of plasma converting enzyme is inhibited for 24 hours and even longer if they are sodium-deplete. In spontaneously hypertensive rats, the antihypertensive effect of perindopril lasts longer than its inhibitory effect on the plasma converting enzyme. This dissociation suggests that the angiotensin-converting enzyme is inhibited in tissues, as has been shown in various tissues including rat kidney and aorta.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

[Renal vasodilator effect of parathormone].

Parathyroid hormone (PTH) has been shown to decrease blood pressure in several animal species and to increase blood flow in different vascular beds. The aim of this work was to characterize and quantify the renal vasodilator effect of PTH on the isolated perfused kidney of the rat. The rat kidney was isolated and perfused in a closed circuit with a modified Krebs-Henseleit solution under non filtering conditions (BSA 10 g/100 ml, ligature of the ureter and perfusion pressure set on 70 mmHg). These conditions have been shown to avoid both glomerular filtration and PTH degradation. Vascular tone of the isolated kidney was restored by a continuous perfusion of prostaglandin F2 alpha (2 x 10(-8) mol/mn). The vasodilator responses to PTH were expressed as a percentage of the relaxation induced on each kidney preparation by 4.4 x 10(-4) M papaverine. PTH fragments [bovine PTH (1-34), NLe8.18Tyr34bPTH (1-34) amide and rat PTH (1-34)] induced concentration-dependent renal vasodilation. When tested at increasing cumulative concentrations, EC50 values ranged from 1 to 2 nM for all PTH fragments; maximal relaxation was obtained at 10(-8) M and only approached 40 p. 100 of the response induced by papaverine. Moreover, at concentrations higher than 10(-8) M, all three peptides induced lower vasodilator responses. Neither indomethacin nor phentolamine modified rPTH (1-34) induced renal response. When rPTH (1-34) was tested as a single concentration on each kidney preparation, a higher maximal response (60 p. 100 relaxation) was obtained. This suggested tachyphylaxis of the renal vasculature to repeated PTH administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

[Vasodilator effect of tertatolol on isolated rat kidney].

Tertatolol, a non cardioselective beta-blocker, maintains or increases renal blood flow in animals and in man. In this work, we confirmed in vitro the renal vasodilator effect of tertatolol and we investigated its mechanism. The rat kidney was isolated and perfused at constant flox in an open circuit with a Krebs-Henseleit solution. A vascular tone was restablished by sequential bolus injections of serotonine (every 5 mn) at a dose increasing perfusion pressure by 40 mm Hg. Tertatolol and other drugs were perfused at increasing concentrations during successive periods of 15 mn. Any relaxation was expressed as percentage inhibition of the initial vaso-constriction induced by serotonine. Tertatolol (3 x 10(-7) to 3 x 10(-5) M) induced a concentration-dependent renal vasodilatation (CI50 = 4.6 +/- 0.4 x 10(-6) M, n = 5) with a maximum effect of nearly 100 p. 100 relaxation. (-) tertatolol and (+) tertatolol were respectively more and less active (CI50 = 1.7 +/- 0.3 x 10(-6) M and 10.6 +/- 2.5 x 10(-6) M, n = 5). Tertatolol metabolites (4-OH tertatolol and sulfoxytertatolol) were inactive, excluding a vascular effect of tertatolol related to its metabolism into vasoactive derivatives. Other beta-blocking drugs, (+/-) sotalol and (+/-) nadolol, were also inactive on the renal vasculature and (-) bunolol only induced renal vasodilatation at concentrations 40 fold higher than that of (-) tertatolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1989

Antihypertensive effect of perindopril: experimental pharmacology.

This review of the pharmacological effects of perindopril based on data in the literature, consists of three approaches: i) demonstration of the antihypertensive effect; ii) characterization of converting enzyme inhibition; iii) understanding of the mechanisms of action. The antihypertensive effect of perindopril has been demonstrated in the spontaneously hypertensive rat and in renovascular hypertension (1 clip-2 kidney or 1 clip-1 kidney). Its intensity and duration are dose-dependent; they are increased in the presence of stimulation of the renin-angiotensin system (renovascular hypertension, sodium depletion). Peripheral vascular resistance is decreased, while cardiac output and heart rate are not increased. This vasodilatation is predominant in the renal vascular bed and is accompanied, in the salt and water restricted dog, by increased sodium excretion. These effects are accompanied by inhibition of the converting enzyme activity. In vitro, perindoprilat (the principal active diacid metabolite of perindopril) is a potent (IC50: 1.5 to 3.2 nM) and relatively specific competitive converting enzyme inhibitor. In vivo, perindopril competitively inhibits the pressor response to angiotensin I. Following a dose of 1 mg.kg-1, the plasma converting enzyme activity is significantly inhibited for 24 hours in the rat and for a longer period in the case of low-salt diet. In the spontaneously hypertensive rat, the antihypertensive effect of perindopril lasts longer than plasma converting enzyme inhibition. This dissociation of the pharmacological effects suggests a role of tissue converting enzyme inhibition, demonstrated in various tissues, including the rat kidney and aorta. Inhibition of the presynaptic effects of angiotensin II on the transmission of sympathetic impulses--demonstrated in pithed rats--and potentiation of the effects of bradykinin--observed in vitro and in vivo--may also be involved in the antihypertensive effect of perindopril.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Binding of loop diuretics to their renal receptors: use as a screening model for potential diuretic activity.

Loop diuretics of the benzoic acid and aryloxyacetic acid families inhibit Na+K+Cl- cotransport. The ranking order of potencies measured in the thick ascending limb of Henle's loop and the ranking order of affinities for [3H]piretanide receptors on renal plasma membranes are the same. Potencies and affinities correlate well (correlation coefficient r = 0.959 for the medulla and r = 0.951 for the cortex). Therefore, measurement of [3H]piretanide binding is proposed to facilitate screening for loop diuretic action.

Animals↗
PubMed1988

[Metabolism and vascular effects of gammaglutamyl L-dopa on the isolated kidney of the rat].

The gammaglutamyl L-dopa (or gludopa), a dopamine (DA) prodrug, may be usefull in antihypertensive therapy as an orally active specific renal vasodilator. Indeed, gludopa is selectively metabolized in vivo by the kidney. This is the consequence of the sequential action of two renal enzymes, gamma-glutamyl transpeptidase (gamma-GT) and aromatic L-amino acid decarboxylase. The aim of this work was to elucidate, in vitro, the factors regulating its metabolism and to characterize its renal vascular effects. The rat kidney was isolated and perfused at constant flow in a closed circuit with a modified Krebs-Henseleit solution (BSA 6g/100 ml). Gludopa injection (10(-5) M) led to generation of DA (measured by gaz chromatography/mass spectrometry) in the venous effluent (134 +/- 39 ng/ml, n = 3) and in the urine (257 +/- 107 ng/mn/g). In non filtering kidneys, the level of DA in recirculating medium was depressed (47 +/- 5 ng/ml, n = 5; p less than 0.05). Glomerular filtration and access to the gamma-GT localized on the brush border membrane of proximal tubular cells are thus important for optimal metabolism of gludopa. Vascular effects of gludopa were studied on the isolated rat kidney after reestablishing vascular tone by continuous perfusion with prostaglandin F2 alpha (10(-8) M/mn) and after inhibition of alpha- and beta-adrenoceptors. Gludopa (3 X 10(-6) to 4 X 10(-5) M) induced dose-dependent renal vasodilation. At 4 X 10(-5) M, the renal response (30 +/- 3 p. 100 of the relaxation induced by 10(-4) M of papaverine) was similar to that elicited by DA at 20 fold lower concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Renal function in patients with obstructive sleep apnea. Effects of nasal continuous positive airway pressure.

Patients with obstructive sleep apnea (OSA) often exhibit nocturnal polyuria, which disappears with nasal continuous positive airway pressure (CPAP) treatment. We measured water and electrolyte urinary excretion, creatinine and osmolal clearances, and water transport during sleep in 13 polygraphically monitored patients with OSA during two consecutive nights, either untreated or treated with nasal CPAP, and in eight normal subjects. Untreated patients with OSA had greater urinary flows and greater urinary sodium, chloride, and potassium excretions than did controls. Nasal CPAP treatment in patients with OSA resulted in a reduction in urinary flow and in sodium and chloride excretion, with a concomitant increase in sodium resorption. None of these effects was observed in CPAP-treated normal subjects. The only effect of nasal CPAP common to normal subjects and patients was a trend toward decreased glomerular filtration rate.

Adult↗
PubMed1987

Renal and iliac vascular effects of dopamine in the anaesthetized rat.

The renal and iliac vascular effects of dopamine were compared in pentobarbital anaesthetized rats. Local vascular resistances were calculated from simultaneous measurement of blood pressure, renal and iliac blood flow. Without pretreatment, dopamine increased renal and iliac vascular resistance. After pretreatment with prazosin, dopamine decreased the renal vascular resistance while the iliac vascular resistance was still increased. After a combination of yohimbine and prazosin pretreatment, dopamine lowered both the renal and iliac vascular resistance by 30%. These responses were not modified by the beta-adrenoceptor antagonist, sotalol, or by pretreating the rats with reserpine. The renal but not the iliac vascular response to dopamine was abolished by (+)-butaclamol, a stereoselective dopamine receptor antagonist, and by SCH 23390, the DA1-selective dopamine receptor antagonist. The decrease in iliac vascular resistance was not modified by indomethacin or the non-selective 5-HT receptor antagonist, metitepin. These results show that after blockade of alpha 1 and alpha 2-adrenoceptors, dopamine induces iliac vasodilation by a postsynaptic mechanism independent of an interaction with beta-adrenoceptors, dopamine or serotonin receptors. They also confirm in the rat in vivo the existence of renal vasodilation mediated by DA1 dopamine receptors.

Adrenergic alpha-Antagonists↗
PubMed1987

Compliance with long-term lithium treatment in major affective disorders.

Compliance with long-term lithium treatment was studied retrospectively in 73 patients suffering from major affective disorders. It was assessed during the first two years treatment by monitoring plasma lithium levels every 6 weeks. 5 patients stopped the lithium treatment before the first two years were up. Of the 68 remaining patients, only 32 (47%) were thought to be complying perfectly. Most of the failures with lithium (11 patients out of 15) were observed in non-compliant patients. The main factors accounting for non-compliance were a low intellectual level, cognitive deficit, affective relapses and traits of personality disorders; on the other hand, neither the age nor the sex of the patients, nor the polarity, the severity or the duration of the affective disorders, nor the modalities or side effects of the treatment seemed to have any bearing on compliance.

Adult↗
PubMed1987

Tissue converting enzyme activity is low in the kidney of spontaneously hypertensive rats.

Angiotensin-converting enzyme (ACE) activity was measured in the plasma, the kidney, and other organs of 5-, 8-, and 11-week-old spontaneously hypertensive male rats (SHR) of the Okamoto-Aoki strain and compared with that of age-matched Wistar-Kyoto (WKY, bred by Iffa-Credo) or normotensive Wistar rats. ACE activity was measured spectrofluorometrically, using the artificial substrate N-CBZ-L-phe-L-his-L-leu. ACE activity was constantly lower in the plasma and renal cortex of SHR from 5 weeks on than in WKY rats. This difference in the renal cortex ACE activity persisted after 1 h of open circuit perfusion of the isolated kidney with Krebs-Henseleit medium. On the other hand, there lung, the brain occipital cortex, or the abdominal aorta of hypertensive or normotensive rats. The percentage inhibition of ACE activity provoked by 7 days of oral administration of ramipril (Hoe 498, 1 mg/kg/day) was analogous in the kidneys and lungs of WKY rats and SHR. Enalapril (MK 421, 30 mg/kg/day) was equipotent to ramipril in the kidney but had lower inhibitory effects on the pulmonary ACE activities of WKY rats and SHR.

Aging↗
PubMed1987

Characterisation of the alpha-adrenoceptors of the rat renal vascular bed.

Postjunctional renal alpha-adrenoceptors were studied (1) in vivo, on the renal vasculature of the anaesthesized rat and compared with those in the femoral vasculature, and (2) in vitro, on the renal vascular bed of isolated perfused rat kidney. In vivo, renal and iliac blood flows were measured with an electromagnetic flow meter. The i.v. injection of (-)-phenylephrine (1-16 micrograms/kg) and B-HT 920 (0.6-600 micrograms/kg) induced an increase in both renal and iliac vascular resistance, inhibited respectively with prazosin (300 micrograms/kg) or yohimbine (300 micrograms/kg). In the kidney, maximum response to B-HT 920 was equivalent to 64% of that to (-)-phenylephrine; on the iliac vasculature, vasoconstrictor responses to both drugs were identical, but only corresponded to 50% of the maximum renal response to (-)-phenylephrine. This indicates the predominance of alpha 1- over alpha 2-adrenoceptors in the renal vascular bed. In vitro, on the isolated perfused rat kidney, vasoconstriction was induced by the preferential alpha 1-adrenoceptor agonists [(-)-phenylephrine, cirazoline and methoxamine] and the preferential alpha 2-adrenoceptor agonists (alpha-methylnoradrenaline, dopamine and clonidine) at concentrations at which they lose their selectivity for the alpha 2-adrenoceptors; all responses were antagonised by prazosin but not by yohimbine. B-HT 920, the selective alpha 2-adrenoceptor agonist, only induced renal vasoconstriction in vitro under concomitant infusion of rabbit plasma.

Animals↗
PubMed1987

Vascular effects of selective dopamine receptor agonists and antagonists in the rat kidney.

The renal vascular effects of dopaminomimetics and dopaminolytics were studied in the isolated perfused rat kidney after pretreatment with phenoxybenzamine (10(-5) M) and sotalol (10(-5) M) and after contraction of the vascular bed with prostaglandin F2 alpha. The DA1- and D1-selective antagonist, SCH 23390, antagonized competitively the relaxation induced by dopamine (pA2 = 9.7 +/- 0.08, m +/- S.D.). On the other hand, (+/-)-DO 710, a D2-preferential benzamide, only antagonized the renal vascular response to dopamine at a concentration 30 times higher than that active on D2 receptors. The ergot derivative, quinpirole, a selective agonist for DA2 and D2 receptors had no renal vascular dopaminomimetic activity, whereas (-)-EOE, a D2-selective ergoline, seemed to be a partial agonist, but 10 times less potent than dopamine. These results confirm the existence of DA1 receptors on the vascular bed of isolated rat kidney but rule out the presence of DA2 receptors. They also reinforce the analogy between DA1 and D1 dopamine receptors.

Animals↗
PubMed1987

[Effects of conversion enzyme inhibitors on the synthesis of angiotensin II by the isolated rat kidney].

On the isolated perfused rat kidney, angiotensin-converting-enzyme activity was evaluated by two approaches: one, biochemical, through the measurements of the enzymatic activity on renal homogenate, the other, pharmacological, through the vasoconstrictor response to angiotensin I. Renal tissue angiotensin-converting-enzyme activity was not modified by setting the kidney under perfusion with a modified Krebs-Henseleit solution but was inhibited after addition of captopril into the perfusion medium (10(-5) M, 100 p. 100 inhibition) or after pretreatment of the animals with ramipril (10 mg/kg/day over 3 weeks, per os, 60 p. 100 inhibition). On the isolated perfused rat kidney, angiotensin I and angiotensin II induced a concentration dependent renal vasoconstriction (EC50 = 1.05 +/- 0.18 X 10(-8) and 0.11 +/- 0.05 X 10(-8) M) which was competitively antagonized by saralasin, an angiotensin II receptor antagonist. Addition of angiotensin-converting-enzyme inhibitors to the perfusion medium (captopril or ramiprilat, 10(-5) M) or pretreatment of the animals with ramipril (50 mg/kg, i.p. the day before or 10 mg/kg/day over 3 weeks, per os) only shifted the angiotensin I concentration-response curve to the right by a factor 3 to 4. The residual vasoconstrictor effect of angiotensin I was abolished by 10(-5) M saralasin and remains linked to a local generation of angiotensin II. Our results suggest that, on the isolated perfused rat kidney, besides the angiotensin-converting-enzyme, an iso-enzyme may also be able to generate angiotensin II.

Angiotensin I↗