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J L Imbs

Publications and source records attributed to J L Imbs.

At least 127 records · Page 7Linked to original sources
PubMed1986

Effect of angiotensin converting enzyme inhibitors on the vasoconstrictor action of angiotensin I on isolated rat kidney.

On the isolated perfused rat kidney, the angiotensin converting enzyme (ACE) activity was evaluated with two approaches: one, pharmacological, through the vasoconstrictor response to angiotensin I (ANG I), and the other, biochemical, through the measurements of the enzymatic activity on renal homogenate. ANG I and angiotensin II (ANG II) induced a concentration-dependent renal vasoconstriction (EC50 = 10.5 +/- 1.8 X 10(-9) and 1.1 +/- 0.5 X 10(-9) M, respectively). Both responses were competitively antagonized by an ANG II receptor antagonist, saralasin (pA2 = 8.65 +/- 0.63 and 8.94 +/- 0.28, respectively). The effects of ACE inhibitors were studied in vitro after addition of captopril and ramiprilat (10(-5) M) directly to the perfusion medium, and ex vivo, after pretreatment of the rats with ramipril (50 mg/kg, i.p. the day before or 10 mg/kg/day, per os, over 3 weeks). In spite of the high doses of ACE inhibitors used, the ANG I concentration-response curve was only shifted to the right by a factor of 4, although renal tissue ACE activity was completely inhibited. Saralasin (10(-5) M) totally abolished the ANG I-induced vasoconstriction elicited in the presence of ACE inhibitors, this response being therefore linked to a generation of ANG II from ANG I. Our results suggest that, on the isolated perfused rat kidney, ANG II may be formed from ANG I by a peptidyl dipeptidase different from the ACE.

Angiotensin I↗
PubMed1986

[Comparison of the vasomotor effects of dopamine on the renal and iliac arterial beds of the anesthetized rat].

Dopamine remains the reference in the study of the mechanisms involved in the antihypertensive effects of dopaminomimetics. Its renal vasodilator effects are well characterized but relaxation of other vascular beds is less known. The iliac vascular response to dopamine was studied in the anesthetized rat (pentobarbital) and compared to the renal response. Simultaneous measurements of arterial pressure, iliac and renal blood flows (electromagnetic flowmeter probes, Skalar, Delft) allowed iliac and renal vascular resistance (IVR, RVR) to be calculated. Their variations were studied after intravenous injections of increasing doses of dopamine (1.5 to 200 micrograms/kg) in unpretreated animals and in animals receiving various pretreatments. Without pretreatment, dopamine induced a biphasic renal response, vasodilation partially masked by subsequent vasoconstriction for doses above 12.5 micrograms/kg of dopamine. Simultaneously, IVR was increased. After alpha-adrenolytic pretreatment (prazosin 2.5 mg/kg, i.v.), dopamine decreased the RVR while iliac vasoconstriction persisted. The association of yohimbine (5 mg/kg, i.v.) to prazosin completely abolished the vasoconstrictive effects: dopamine lowered then by about 30% both IVR and RVR. Dopamine-induced iliac and renal decrease in vascular resistance persisted in the presence of a beta-adrenoceptor antagonist [+/-)-sotalol 30 mg/kg, i.v.), after depletion of catecholamines from sympathetic terminals (reserpine 10 mg/kg, i.p. 20 h before the experiment) or inhibition of cyclo-oxygenase (indomethacin 2.5 mg/kg, i.p. 20 h and 1 h before dopamine). On the contrary, a specific antagonist of dopamine receptors, (+)-butaclamol (60 micrograms/kg/min, i.v.) stereoselectivity inhibited the dopamine-induced renal vasodilation but did not modify the iliac response.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗
PubMed1986

[Diuretics].

Microaspiration techniques and clearance studies have shown that reabsorption of filtered sodium approximates 65% in the proximal tubule, 25 to 30% in the ascending limb of the loop of Henle and 5 to 10% in the dilution segment. Reabsorption in the Henle loop is of special significance as it governs the process of dilution-concentration of urine. Moreover, inhibition of sodium reabsorption in the loop of Henle necessarily produces a substantial loss of sodium since only a fairly small fraction of urinary sodium is reabsorbed beyond the Henle loop (dilution segment, distal tubule). Excretion of water and electrolytes is regulated by humoral factors, such as the renin-angiotensin-aldosterone system, some prostaglandins and certain kinins. Factors that promote excretion of sodium, produced in particular by the myocardium, have recently been demonstrated. The correlation between blood pressure and salt has been substantiated by many findings. Diuretics are commonly used to treat high blood pressure as well as edema. Recent evidence indicates that sodium transport is altered in idiopathic hypertension, at least in red blood cells. Clinical trials of diuretics are designed to localize the drug's action and quantify its saluretic activity (evaluation of potency and effectiveness--single doses, sustained treatment). Furthermore, the minimal efficient antihypertensive dosage should be determined. Diuretics can be divided into two groups according to whether they produce an increase or decrease in serum potassium. Diuretics that are capable of producing hypokalemia belong to two main families. One consists of the Henle loop diuretics that interfere with the mechanisms of dilution-concentration of urine. Action of these drugs is potent and short-lived. For instance, following a single dose of furosemide, excretion of sodium can reach 25-30% of filtered sodium; renal blood flow increases; CH2O and TCH2O decrease. With furosemide, induction of diuresis is rapid (within a few minutes after IV injection and 20 mn after oral ingestion); elimination half-life is 50 mn; absolute bioavailability is 50-70%; 95% of the drug is bound to plasma proteins; elimination is mainly through the kidneys. Other Henle loop diuretics include ethacrynic acid, whose elimination half-life is less than one hour; bumetanide, which is 40 times more potent than furosemide; muzolimine, whose action is more lasting despite the fact that only 65% of the drug is bound to plasma proteins; and ozolinone, which has a saliuretic action comparable to that of furosemide and in addition exerts a direct vasodilating effect.(ABSTRACT TRUNCATED AT 400 WORDS)

Acid-Base Equilibrium↗
PubMed1986

[Detection of drug-induced nephrotoxicity].

This is a report of a round table organized during the second meeting of Clinical Pharmacology held in Giens (France) in September 1985. At the beginning of the meeting, the clinical aspects of drug-induced nephrotoxicity were reviewed. Thus we tried to precise the real interest of the studies of proteinuria, urinary cytology, enzymuria and fractional clearances of lithium or magnesium. The most interesting part of our discussions was to know the point of view of men working in drugs companies when a renal abnormality is found during a clinical trial of a drug and when previous experimental studies did not find any renal adverse effects of the drug. It was suggested in a such situation to do particular studies. Methods generally used to study renal physiology as autoradiography micropuncture, microinjection had to be performed to localize the action of the drug along the nephron. It was also discussed of the use of isolated perfused kidney as a tool in drug disposition and the use of renal cells culture. A better understanding of the mechanisms of direct renal toxicity of drugs was obtained from the results of experimental models. It is not so easy, at the present time, to know the mechanisms of immunological drug-induced nephrotoxicity. It seems necessary to develop new experimental models. The results obtained in animals with Cl2Hg or D. Penicillamine or gold salts afford to suspect some mechanisms for these types of nephropathies. This aspect of drug induced nephropathy is more complex because there is a large interindividual variation in susceptibility to these drugs.

Animals↗
PubMed1985

Characterization of a high affinity piretanide receptor on kidney membranes.

The tritiated loop diuretic, piretanide, is a useful ligand for specific diuretic receptors which are present in the plasma membranes of renal medullary cells. Its high specific activity (30 Ci X mmol-1) made it possible to demonstrate the existence of a high affinity receptor (Kd approximately 5 nM) and a binding site with low affinity. High affinity binding is saturable, reversible and displaceable by a number of non-radioactive loop diuretics. Structural analogues, devoid of diuretic activity, do not displace piretanide binding. No specific binding occurs in liver or spleen membranes.

Animals↗
PubMed1985

Loop diuretics bind to distinct receptors in renal medulla and cortex.

Receptors which bind [3H]-piretanide were demonstrated on membranes prepared from renal medulla and cortex. They exhibit all the characteristics of a specific receptor such as high affinity, specificity, tissue selectivity, reversible binding kinetics and proportionality between affinity and diuretic effect. Medullary and cortical receptors are clearly distinct since they have different ion requirements.

Animals↗
PubMed1984

Effect of captopril on intrarenal blood flow.

The inhibition of the renin-angiotensin system by captopril was used in pentobarbital-anesthetized dogs to confirm that the vasoconstrictive action of endorenally synthesized angiotensin II predominates on the efferent glomerular arteriole. Ozolinone is a loop diuretic with two isomers. Only (-)- ozolinone is diuretic, whereas both isomers have a renal vasodilatory effect which predominates on the efferent glomerular arteriole. Only the diuretic isomer increases renin release. The renin hypersecretion is simultaneous with recovery from the initial fall in filtration fraction, because of postglomerular vasodilatation. This recovery does not occur with (+)- ozolinone and is inhibited by pretreatment with captopril. This confirms that vasoconstrictive action of angiotensin II predominates on the efferent glomerular arteriole. Such a vasoconstrictive effect might affect blood flow in the vasa recta, which arise from the efferent arterioles of juxtamedullary glomeruli. This action might enable the renin-angiotensin system to participate in the control of renal medullary blood flow and urinary concentration.

Animals↗
PubMed1984

Modulation of renal ATPase activities by cyclic AMP.

A possible link between cellular cyclic AMP content and Na+K+ATPase activity was investigated in homogenates of rat kidney. Enzyme kinetics of Mg2+ and Na+K+ATPase were run in the presence of cyclic AMP, dibutyryl cAMP and compounds expected to elevate cyclic AMP levels such as forskolin, a potent adenylate cyclase activator, IBMX, an inhibitor of phosphodiesterases, and the beta-agonist isoproterenol. Medullary Na+K+ATPase is strongly inhibited by cyclic AMP whereas cortical Na+K+ATPase was stimulated in the same conditions. The correlation between ATPase activity and cellular cyclic AMP content supports the concept of a possible regulation of the enzyme by cyclic AMP.

1-Methyl-3-isobutylxanthine↗
PubMed1984

Vascular effects of apomorphine and related compounds in the perfused rat kidney.

The renal vascular effects of aporphines and related compounds were studied on the isolated perfused rat kidney in the presence of 10(-5) M phenoxybenzamine and 10(-5) M sotalol and after contraction of the vascular bed with prostaglandin F2 alpha (10(-7) -3 X 10(-6) M). Under these conditions, (R)-(-)-apomorphine showed renal dopaminomimetic activity, i.e. renal vasodilation competitively inhibited by (+)-butaclamol (10(-8) M) but not by (-)-butaclamol (3 X 10(-8) M). It had an apparent affinity 25 times higher but a markedly lower intrinsic activity than dopamine. N-n-Propyl and trihydroxylated aporphines were less potent and the mono-10-hydroxylated aporphine was completely inactive. (S)-(+)-Bulbocapnine also showed weak dopaminomimetic activity but tetrahydropapaveroline was devoid of such an effect. (-)-N-(2-Chloroethyl)-norapomorphine (10(-5) M) irreversibly antagonised dopamine-induced renal vasodilation. At concentrations above 3 X 10(-6) M, most aporphines and tetrahydropapaveroline induced additional non-dopamine receptor related renal vasodilation.

Animals↗
PubMed1984

The sympathetic nervous system and renal sodium handling: is dopamine involved?

The presence of vascular dopamine receptors and dopaminergic nervous fibers in the kidney suggests that dopamine plays a role in the control of renal function by the autonomic nervous system. Dopamine and norepinephrine have contrary effects in the kidney. This is particularly apparent at the level of efferent glomerular arterioles. Variations in postglomerular vascular resistance may induce variations in the filtration fraction and in peritubular oncotic pressure, thus influencing proximal tubule sodium reabsorption. We propose that the sympathetic innervation of the kidney controls the postglomerular vascular resistance; this control can be achieved through a balance between the vascular effects of dopamine and norepinephrine.

Animals↗
PubMed1984

[Characterization of the alpha adrenoreceptors in the vascular bed of the isolated rat kidney].

The vasoconstrictive effect of alpha-adrenoceptor agonists was studied on isolated perfused kidney from normal Wistar rats. Methoxamine (ED50 = 1.61 +/- 0.16 X 10(-6) M; m +/- SEM), phenylephrine (2.33 +/- 0.16 X 10(-6) M) and alpha-methylnoradrenaline (1.60 +/- 0.40 X 10(-6) M) acted as full agonists. Dopamine (9.5 +/- 1.08 X 10(-5) M) had a partial agonistic effect. Clonidine and B-HT 920 were inactive up to the concentration of 10(-4) M. Prazosin, but not yohimbine (10(-6) M) antagonized the response to phenylephrine (pA2 = 8.48 +/- 0.12) and to alpha-methylnoradrenaline (8.02 +/- 0.10). Our results suggest that the postsynaptic alpha-adrenoceptors which when stimulated increases vascular resistance of isolated rat kidney, belong exclusively to the alpha 1-subtype.

Adrenergic alpha-Agonists↗
PubMed1984

[Practical value of the assay of serum angiotensin converting enzyme activity in sarcoidosis].

Serum levels of angiotensin conversion enzyme (A.C.E.) are increased in 60 to 80% of cases of sarcoidosis. A.C.E. levels were measured as part of the initial assessment of 70 patients with the disease, with repeated measurements in 18 of them. The subsequent course of sarcoidosis was evaluated over a minimum period of 7 months, in relation to initial serum A.C.E. levels. A high serum A.C.E. level is indicative of the secretion of the cells of the epithelioid and giant cell granuloma and reflects the activity of the disease at the particular time without providing any definite prognostic information. Study of 6 patients treated with corticosteroids showed that serum A.C.E. levels rose again when treatment was reduced or stopped in 4 of them, this renewed rise appearing to precede the radiological recurrence. Whilst the prognostic value of alveolar lymphocytosis is greater than that of serum A.C.E. levels in sarcoidosis, measurement of serum A.C.E. is easier in the context of therapeutic surveillance.

Humans↗
PubMed1984

Is the renin-angiotensin system involved in urinary concentration mechanisms?

Renin release elicited by i.v. injection of loop-diuretics was used to study the effects of angiotensin II (AII) on intrarenal hemodynamics. The vasoconstrictive action of intrarenally synthesized AII predominates in the efferent glomerular arteriole. Such a vasoconstrictive effect could affect blood flow in the vasa recta which stem from efferent arterioles of juxtamedullary glomeruli. Renin secretion and renal inner medullary blood flow (tissue clearance of 133Xe) were simultaneously measured before and after frusemide-induced renin release. The relationship between renin secretion and renal inner medullary blood flow was inverse. Changes in renal medullary blood flow may be physiological determinants of medullary osmolality and renal concentration ability. The intrarenal role of AII in urinary concentration recovery after frusemide was examined. Inhibition of renin release by propranolol or AII-blockade (by saralasin or Hoe 409) delayed recovery of urinary osmolality. In the conscious rat, propranolol slowed down recovery of the cortico-papillary gradient for sodium. Its vasoconstrictive action on the efferent glomerular arteriole might enable the renin-angiotensin system to participate in the control of renal excretion of salt and water.

Angiotensin II↗