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J L Imbs

Publications and source records attributed to J L Imbs.

At least 145 records · Page 8Linked to original sources
PubMed1983

[Pharmacologic characteristics of renal dopaminergic receptors: therapeutic perspectives].

The effects of dopamine (DA) on the smooth muscle fibres of the renal vascular bed are complex. They involve the postsynaptic alpha- and beta-adrenoceptors as well as the dopamine ones. On denervated kidney, in presence of alpha- and beta-blockers, intrarenal DA perfusion provokes vasodilation, increases natriuresis and stimulates renin secretion. The vasodilator effect of DA on the renal vascular bed was studied thanks to an isolated perfused rat kidney preparation which, when high concentrations of phenoxybenzamine and sotalol were present, made it possible to measure the effect of dopaminomimetics and dopaminolytics on the renal vascular resistance of a kidney previously vasoconstricted by continuous PGF2 alpha perfusion. (+)--Butaclamol and cis-flupenthixol proved to be invaluable tools to demonstrate the specificity of the dopamino-agonists response, since both shift the dose-response curve according to the criteria for competitive antagonism at doses at which their isomers are not active (fig. 2). Thus, it was possible to calculate the apparent pA2 for the various dopaminolytics and to classify them according to their affinity for the renal vascular dopamine receptors. Table 1 gives the classification. Flupenthixol, which has only a low affinity for the alpha 2-adrenoceptors, already inhibits the vasodilator effect of DA at 10(-8) M. The low stereospecificity of the enantiomers of sulpiride allows a distinction to be drawn between the "postsynaptic" vascular dopamine receptors and the presynaptic ones. The agonists of the renal vascular dopamine receptors provoked dose-dependent renal vasodilation on our preparation when phenoxybenzamine and sotalol were present and this was stereoselectively inhibited by (+)-butaclamol. Table II shows the activity of the dopaminomimetics meeting these criteria. p-Tyramine, di-propyl-m-tyramine and RU 24926 proved to have no dopaminomimetic effect. Their lack of activity seems to be attributable to the suppression of the hydroxyl in position 4. Mesenteric, splenic or cerebral artery preparations were also used to characterize the vascular dopamine receptors : tables III and IV compare the results taken from the literature. The classification obtained tallies quite well which suggests that the dopamine receptors located in the various vascular beds are identical. We compared the characteristics of the renal vascular dopamine receptor established from isolated rat kidney, with three other pharmacological models of dopamine receptor : the activation of dopamine-sensitive adenylate cyclase, the presynaptic modulation of the transmission of the sympathetic influx, and prolactin release (Table V).(ABSTRACT TRUNCATED AT 400 WORDS)

Anesthesia↗
PubMed1982

Vasodilator effects of dopaminomimetics in the perfused rat kidney.

The renal vascular effects of dopaminomimetics were studied in the isolated perfused rat kidney after pretreatment with 10(-5) M phenoxybenzamine and 10(-5) M sotalol and after contraction of the vascular bed with prostaglandin F2 alpha (10(-7) to 3 x 10(-6) M). Under these conditions, our criterion for vascular dopaminomimetic activity was renal vasodilation, competitively inhibited by d-butaclamol (10(-8) M) but not by 1-butaclamol (3 x 10(-8) M). Dopamine is active at micromolar concentrations (ED50 = 2.53 +/- 0.34 x 10(-6) M). The N-alkylated analogues of dopamine preserve this activity if the alkyl group is a methyl group (epinine) or two n-propyl groups (di-n-propyl-dopamine). The catechol nucleus appears essential for renal vascular dopaminomimetic activity (SK&F 38393, active; p-tyramine, di-n-propyl-m-tyramine and RU 24926, inactive). Bromocriptine reproduces renal dopaminergic vasodilation with an ED50 of 1.3 +/- 0.14 x 10(-6) M. The study of structure-activity relationships of dopaminomimetics relates the vascular dopamine receptor, associated with renal vasodilation, to the dopamine receptor, associated with stimulation of dopamine-sensitive adenylate cyclase.

Animals↗
PubMed1982

Variance comparison as a tool in clinical pharmacology: an example with two loop diuretics.

Comparison of variances can be usefUl in assessing the regularity of drug effects. In order to compare the variances of the saluretic effects of piretanide and frusemide, two loop diuretics with different bioavailabilities, a double-blind cross-over study was carried out in 34 normal volunteers. The diuretics were given in randomized order, with an interval of 7 days, in single equipotent doses (frusemide 6.25 mg and piretanide 1.0 mg chosen from previous results) adjusted by body weight. The dispersion of individual values (comparison of variances from paired measures) for Na+, Cl- and Ca++ excretion, urine osmolality and excretion of the drugs, was significantly smaller for piretanide than for frusemide. It is concluded that the saluretic effect of a single dose of piretanide varies less than that of an equipotent dose of frusemide. The methodology may be useful in trials of drugs for which regularity of effect is important.

Biological Availability↗
PubMed1981

[Effect of propranolol on diuretic activity of furosemide hypertensive patients (author's transl)].

The effect of propranolol on water and sodium depletion provoked by frusemide was studied. Nine hypertensive patients were treated at 2-day intervals with a single dose of 40 mg of frusemide associated with a placebo or propranolol (320 mg given in 8 doses over a period of 24 hours). The association frusemide-propranolol is more hypotensive than frusemide alone. Propranolol reduced the rise in plasma renin activity and aldosteronuria provoked by the diuretic; total sodium output/24 h remained stable but sodium elimination was increased in the later samples. This prolongation of the natriuretic action is correlated with the inhibition of hyperaldosteronuria. Propranolol depresses urinary osmolality for a longer period than frusemide alone and water elimination tends to be higher. This action of the beta-blocker on urine concentration is independent of its effects on aldosteronuria but is correlated with the inhibition of the rise in plasma renin activity.

Aldosterone↗
PubMed1980

Effects of indomethacin and methylprednisolone on renal elimination of lithium in the rat.

Wistar rats were given lithium chloride (16.7 mg/kg i.p.) after treatment with indomethacin (2.5 mg/kg/day for 5 days), with methylprednisolone (3 mg/kg/day for 5 days), or with their solvents. Lithium and creatinine clearance and urinary elimination of sodium and phosphate were determined. Indomethacin increases while methylprednisolone decreased the fractional tubular reabsorption of lithium. The quantity of lithium eliminated in the urine is correlated with the urinary elimination of sodium and phosphate. The effects of the anti-inflammatory drugs on renal elimination of lithium seemed linked to their effects on proximal sodium reabsorption.

Animals↗
PubMed1980

[Lithium elimination by the isolated perfused rat kidney (author's transl)].

The pharmacokinetics of lithium, a drug with a narrow therapeutic index, depends on the renal elimination of the metal. An open circuit, constant flow isolated rat kidney preparation perfused with gelatinized (Haemaccel) Krebs-solution, was used to study the urinary elimination of lithium relative to sodium. A series of 88 kidney preparations perfused with a solution containing 0.47 mmol/l lithium was compared to another of 52 kidney preparations perfused without lithium. Lithium reduced the tubular reabsorption of sodium but did not modify the elimination of potassium. There is a strong correlation between the tubular reabsorption of lithium and of sodium. The correlation between tubular reabsorption of lithium and filtered load demonstrates the existence of a glomerulo-tubular balance.

Animals↗
PubMed1978

Intrarenal control of urine concentration by angiotensin II.

1. The intrarenal role of angiotensin II in the recovery of urinary concentration after frusemide was examined in anaesthetized dogs by the intrarenal infusion of angiotensin II antagonists. 2. Renin secretion and renal inner medullary blood flow (tissue clearance of intraparenchymatously injected 133Xenon) were simultaneously measured before and 3 h after frusemide injection. 3. Intrarenal angiotensin II blockade delayed the recovery of urinary osmolality after frusemide. 4. An inverse relationship was found between renin secretion and renal inner medullary blood flow.

Angiotensin II↗
PubMed1978

[The effects of phenylbutazone on the decrease of lithium clearance].

During the treatment of a manic depressive patient, the authors reported some lithium toxicity signs, as lithium carbonate (3 X 300 mg p.d.) and phenylbutazone suppository (3 X 250 mg/p.d.) were associated, this last medication being prescribed for a phlebitis. Lithiemia increased from .70 to 1,44 mEq/l., the lithiemia clearance falling from 10 ml to 5 ml/mn/1.73 m2) and the lithium tubular reabsorption percentage increasing from 85 to 94% (standard rates: 77.4 +/- 1.3%). In a second time, a rat experimentation corroborated these findings: phenylbutazone treatment (100 mg/kg/p.o. for five days) resulted in a lithium tubular reabsorption increase. It seems that the association of lithium carbonate with phenylbutazone should be avoided. The authors point out the risk of prescribing lithium and pyrazolic by-products as phenylbutazone, which are potentially nephrotoxic.

Animals↗
PubMed1977

Comparison of the effect of two groups of diuretics on renin secretion in the anaesthetized dog.

1. The effects of two groups of diuretics on renin secretion have been compared in dogs anaesthetized with pentobarbital. 2. Frusemide, ethacrynic acid and bumetanide cause an immediate rise in renin secretion which is not inhibited either by DL-propranolol or by a bilateral ureterovenous anastomosis which prevents salt and water loss. 3. Clopamide, metolazone and indapamide do not cause an immediate rise in renin secretion. Renin hypersecretion is induced only 1 h after intravenous injection of these diuretics. 4. Renin secretion was studied for 6 h after frusemide injection: the immediate rise was followed by a later increase in renin secretion. This later rise was inhibited by propranolol and by ureterovenous anastomosis. 5. These results allow us to distinguish between a direct renal mechanism responsible for early renin hypersecretion, which appears to be connected with the action of the diuretic on the ascending limb of Henle's loop, and an indirect mechanism responsible for late renin hypersecretion, which appears to be connected with salt and water loss.

Animals↗
PubMed1977

A potent new beta2-adrenoceptor blocking agent.

1 (t-Butyl-amino-3-ol-2-propyl) oximino-9 fluorene is a new beta2-adrenoceptor blocking agent with a pA2 of 9.23+/-0.25 on isolated trachea. 2 It provokes hypertension in normotensive rats and does not prevent arterial hypertension in SHR rats, although it does prevent the renin secretion normally induced by isoprenaline infusion.

Adrenergic beta-Antagonists↗