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C Guilmard

Publications and source records attributed to C Guilmard.

12 recordsLinked to original sources
PubMed1998

Comparison between endothelial and neuronal nitric oxide pathways in rat aorta and gastric fundus.

This study examines the ability of different nitric oxide synthase (NOS) inhibitors and NO donors to inhibit the endothelium-dependent relaxation of the rat aorta and the NANC relaxation of the rat gastric fundus. NG-Nitro-L-arginine, N-monomethyl-L-arginine, and S-methyl-L-thiocitrulline elicite comparable potency in the aorta and in the fundus. However, 1-(2-trifluoromethyl)imidazole (TRIM), unlike 7-nitroindazole, is more potent on the fundus than on the aorta, showing that TRIM elicits a selective functional inhibition of the neural NOS isoform. (1H)-(1,2,4)Oxadiazole(4,3-a)quinoxalin-1-one, a selective inhibitor of soluble guanylyl cyclase, inhibits the dilator response in both tissues and the cyclic GMP mimetic, 8-Br-cGMP, is 16 times more potent for inducing relaxation in the gastric fundus than in the aorta. However, methylene blue and LY-83583, two other inhibitors of soluble guanylyl cyclase and superoxide anion-generating agents, are at least 100 times less potent on fundus strips than on aortic rings. The data suggest that once released into the extracellular space, NO is more susceptible to inactivation by superoxide anions in the vascular tissue than in the gastric fundus. Thus, the study shows that selective inhibition of NO in a target tissue may be reached not only at the NOS isoform level but also by the manipulation of the NO pathway.

Animals↗
PubMed1996

Pharmacological characterization of alpha 1-adrenoceptor subtype mediating regulation of arterial pressure and urethral perfusion pressure in the anaesthetized rat.

1. The alpha 1-adrenoceptor subtypes mediating the regulation of arterial pressure (AP) and urethral perfusion pressure (UP) in the anaesthetized rat were characterized by using selective alpha 1-adrenoceptor agonists and antagonists. 2. Intravenous administration of selective alpha 1-adrenoceptor agonists elicited a dose-dependent increase in AP and UP. The rank order of agonist potency: oxymetazoline (ED50, 6.2 and 8.2 nmol kg-1 > phenylephrine (ED50, 32 and 27 nmol kg-1 > methoxamine (ED50, 300 and 296 nmol kg-1 was the same for AP and UP, respectively. 3. The effects of phenylephrine on AP and UP were antagonized, in a dose related-manner, by pretreatment with alfuzosin, BMY 7378, 5-methyl-urapidil, phentolamine, prazosin, spiperone and WB 4101.5-methyl-urapidil was the only alpha 1-adrenoceptor antagonist more potent on UP than on AP. 4. The potency of the different alpha 1-adrenoceptor antagonists tested on AP and UP was significantly correlated with their binding affinity for the expressed recombinant alpha 1a-, but not alpha 1b- or alpha 1d-, adrenoceptor subtype. 5. The results suggest that in the anaesthetized rat (1) both AP and UP are regulated by the alpha 1A-adrenoceptor subtype; and (2) the urogenital selectivity of 5-methyl-urapidil may be due to the existence of multiple forms of the alpha 1A-adrenoceptor.

Adrenergic alpha-Agonists↗
PubMed1994

Effect of the platelet activating factor antagonist BN52021 in rabbits: role in gentamicin nephrotoxicity.

Platelet activating factor (PAF) is an ubiquitous phospholipid that acts as a mediator of numerous pathophysiological conditions, including drug nephrotoxicity. Aminoglycosides are potent antibiotics but their use is limited by their nephrotoxic potential. We assumed that PAF could participate in inducing gentamicin nephrotoxicity, and we used the PAF antagonist BN52021 to test this hypothesis. We studied renal glomerular and tubular function by clearance techniques and renal histology in four groups of New Zealand male rabbits treated for 7 days with isotonic saline, BN52021, gentamicin, or gentamicin + BN52021. BN52021 alone reduced only fractional excretions (FE) of sodium and chloride, without modifying the other parameters studied. Renal histology was not altered. Gentamicin reduced glomerular filtration rate and renal plasma flow. Free water clearance was not modified. Sodium, potassium, chloride, calcium, and magnesium FEs were raised. Renal histology showed a massive and diffuse tubular necrosis. BN52021 did not modify gentamicin glomerular, tubular, or histopathological alterations. These data suggest that PAF might physiologically affect tubular function in New Zealand male rabbits, increasing sodium and chloride excretions, and in a minute manner, potassium, calcium, and magnesium excretions. Under our experimental conditions, there was no evidence for a role of PAF in gentamicin nephrotoxicity.

Animals↗
PubMed1994

Endothelin receptor subtypes A and B are up-regulated in an experimental model of acute renal failure.

The two endothelin (ET) receptor subtypes (ETA and ETB) have been characterized in rat kidney from normal rats and rats with acute renal failure induced by hypertonic glycerol administration. In control rats, the total number of ET receptors in kidney cortex and medulla was 155 and 386 fmol/mg of protein, respectively. The ratio of ETA to ETB receptors was 54:46 in renal cortex and 35:65 in renal medulla. Treatment of rats with 10 ml/kg glycerol (50%, w/v) intramuscularly resulted in severe renal dysfunction; the serum urea concentration increased from 0.46 to 2.65 g/liter and the creatinine clearance decreased from 1.06 to 0.30 ml/min. Ligand binding studies showed that glycerol-induced acute renal failure was associated with a marked up-regulation of ETA and ETB receptor subtypes in both cortex and medulla. In glycerol-treated rats, the total ET receptor density in kidney cortex and medulla was increased to 294 and 1172 fmol/mg of protein, with ETA/ETB ratios of 52:48 and 31:69, respectively. The upregulatory effect of glycerol treatment was significantly more pronounced in renal medulla than renal cortex and affected ETB receptors preferentially, compared with ETA receptors. Subsequently, ETA and ETB receptor mRNA levels were markedly increased by glycerol administration in both kidney cortex and medulla, as assessed by polymerase chain reaction coupled to reverse transcription. These results suggest that up-regulation of renal ET receptors, particularly ETB receptors in kidney medulla, may account for or contribute to renal function impairment induced by glycerol, and they support a pathophysiological role for ET in acute renal failure.

Acute Kidney Injury↗
PubMed1993

Upregulation of renal endothelin receptors in glycerol-induced acute renal failure in the rat.

Acute renal failure was induced in rat with a hypertonic glycerol solution and endothelin-1 (ET-1) binding was measured in kidney membrane preparations. In control animals, [125I]-ET-1 bound to specific recognition sites in kidney cortex (Bmax = 134 +/- 11 fmol/mg protein) and medulla (Bmax = 300 +/- 9 fmol/mg protein) with an apparent dissociation constant (Kd) of 0.16 +/- 0.06 nM and 0.39 +/- 0.07 nM for cortex and medulla, respectively. A single i.m. dose of 10 ml/kg glycerol (50% w/v) resulted in alterations of renal function that were maximal 48 h after glycerol administration. After this 48-h period, serum urea was increased from 0.20 +/- 0.01 g/L to 1.16 +/- 0.20 g/L (p < 0.001) and creatinine clearance was reduced from 1.04 +/- 0.15 ml/min to 0.23 +/- 0.06 ml/min (p < 0.001). Renal ET-1 receptor density was significantly increased in glycerol-treated rats to 255 +/- 14 fmol/mg protein in renal cortex (p < 0.01), and 576 +/- 55 fmol/mg protein in renal medulla (p < 0.01), with no significant modification of the Kd values. These results suggest that upregulation of ET-1 receptors is involved in renal hemodynamic impairment induced by glycerol.

Acute Kidney Injury↗
PubMed1990

Involvement of endothelin in renal processes.

This study examined the effect of various doses of endothelin (from 0.2 to 2 nmol/kg body wt) on regional hemodynamics in conscious unrestrained rats. Normal rats were instrumented chronically with femoral artery and vein catheters and pulsed Doppler flow probes simultaneously on the renal and superior mesenteric arteries and the abdominal aorta. Endothelin induced a biphasic response of mean arterial pressure. First, endothelin provoked a sharp hypotension with tachycardia, vasodilation of the hindquarter, and a pronounced decrease in renal and mesenteric blood flows. After this initial response, endothelin induced a dose-dependent increase of mean arterial pressure. Changes in the hindquarter vascular resistance were less pronounced than those in renal and mesenteric vascular resistances. Endothelin (2 nmol/kg) reduced renal flow (-86%) resulting from a vasoconstriction (+1,818%) significantly more pronounced than for the mesenteric vascular bed. In another set of experiments, endothelin (2 nmol/kg) induced an increase in proteinuria, characterized by an increase in excreted albumin and by the appearance of proteins with molecular weights of 20,000-280,000. Renal vascular bed exhibited a pronounced sensitivity to the vasoconstrictive effect of endothelin associated with changes in renal function.

Animals↗
PubMed1990

Platelet-activating factor antagonist, BN-52021 protects against cis-diamminedichloroplatinum nephrotoxicity in the rat.

The protective effect of the platelet-activating factor (PAF) antagonist, BN 52021, was assessed on cis-diammine-dichloroplatinum (CDDP)-induced nephrotoxicity. Wistar male rats were treated with either a single dose of CDDP (10 mg/kg b.w. ip) alone or in association with 7 daily doses of BN 52021 (10 mg/kg b.w. ip). At the end of the experiment, the CDDP-treated rats lost 25% of body weight and serum creatinine and urea increased from 0.041 +/- 0.006 mmol/l and 0.165 +/- 0.007 g/l for the control group to 0.202 +/- 0.019 mmol/l and 1.51 +/- 0.131 g/l versus CDDP respectively. Body weight, serum creatinine, serum urea and creatinine clearances were similar to the control group in animals treated with CDDP and BN 52021. CDDP caused proximal tubular necrosis and dilatation of cortical collecting tubes, changes that were markedly less in the BN 52021-protected animals. The concomitant administration of BN 52021 with CDDP did not modify the plasma pharmacokinetic of CDDP. In addition, BN 52021 did not interfere with the antiproliferative and antitumoral actions of CDDP in cultured human tumor cells. BN 52021 therefore could prevent the nephrotoxicity of CDDP.

Acute Kidney Injury↗
PubMed1990

[The impact of endothelin on renal hemodynamics in conscious rats].

Endothelin (ET), a peptide recently isolated from the supernatant of cultured endothelial cells, is the most potent vasoconstrictive and hypertensive agent known up till now. We have examined the effect of ET-1 intravenous injection on regional hemodynamics in conscious unrestrained rats. Normal rats are instrumented with an arterial catheter for measurement of mean arterial pressure (MAP) and with pulsed Doppler flow probes on renal and mesenteric arteries and the abdominal aorta for simultaneous recording of blood flow velocities (V). These parameters allow calculation of vascular resistance (R) (R = MAP/V). Thus, ET-1 induces an initial and sharp hypotension, concomitant with tachycardia and a marked vasoconstriction of renal and mesenteric arteries, but a vasodilatation of aorta. This response is followed by a dose-dependent and long-lasting increase of MAP and of renal, mesenteric and aortic vascular resistances accompanied by a decrease of heart rate. The greatest impact of ET-1 constrictive effects is seen on the renal vascular bed whereas the abdominal aorta appears to be far less sensitive. In fact, the dose of 2 nmol/kg of ET-1 induces a dramatic and long-lasting fall of renal blood flow (-86%) resulting from an important vasoconstriction (+1818%). Finally, an elevation of proteinuria is revealed in ET-1 (2 nmol/kg) treated rats, but not in those treated with the same dose of Angiotensin II. This proteinuria is characterized by the appearance of proteins with a molecular weight from 20,000 to 140,000 and sometimes 280,000, and an increase of excreted albumin, seeming to reflect an alteration of glomerular permeability.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

[Renal diseases and platelet activating factor].

The platelet-activating factor (PAF) is a molecule produced by several types of cells (monocytes, platelets, polynuclears, eosinophils and endothelial cells) and by different organs (lungs, heart, kidney). Its action concerns many inflammatory phenomena such as allergy, cerebral, cardiac or renal ischemia. The discovery of specific antagonists helped us to understand the pathophysiological effects of PAF in man. As PAF is involved in the mechanism of proteinuria and many other nephropathies, the use of antagonists for the treatment of such disorders seems valuable.

Acute Kidney Injury↗
PubMed1988

Protection of platelet-activating factor-induced acute renal failure by BN 52021.

Although platelet-activating factor (PAF) is a well-known mediator in experimental shock, its precise role in acute renal failure remains to be defined. Male Wistar rats (209 +/- 12 g) were placed in individual metabolic cages for 24 h before i.v. injection of PAF (2-6 micrograms/kg). Injection of 6 micrograms/kg PAF proved lethal and use of such a high dose was thus discontinued. Administration of 2 micrograms/kg and 4 micrograms/kg PAF resulted in a fall of glomerular filtration rate (GFR) associated with a reduction in urinary flow rate (UFR). Rats pretreated with BN 52021 (25 mg/kg p.o.) exhibited values of GFR similar to that of the control group, but not after 4 micrograms/kg PAF. In addition, in the group of BN 52021 pretreated rats and injected with 2 micrograms/kg or 4 micrograms/kg PAF, UFR was not significantly different from that of the control group at 24 h. Examination by electron microscopy revealed the presence of platelets in the glomeruli, as well as loss of fixed anionic charges in PAF injected rats. The presence of these platelets was not observed in rats treated with BN 52021 and injected with PAF. No changes in GFR and UFR were observed at 6 h or 24 h in vehicle or BN 52021 treated rats. Thus, BN 52021 which affords protection against acute renal failure induced by PAF may be of therapeutic value in other types of kidney disease in which this mediator is active.

Acute Kidney Injury↗
PubMed1987

Inhibition of rat endotoxin-induced lethality by BN 52021 and BN 52063, compounds with PAF-acether antagonistic effect and protease-inhibitory activity.

Since proteolytic enzymes play a key role in endotoxaemia and anaphylaxis, diseases in which PAF-acether may be involved, we have investigated the activity of BN 52021 and BN 52063, two potent and specific PAF-acether antagonists, on plasma protease activity in the rat. After oral administration, both drugs dose-dependently decreased plasma trypsin-like activity (PTLA) although they did not show any inhibitory effect in vitro. PAF-acether and endotoxin injected into rats increased PTLA, the increase with endotoxin appearing more slowly but to a higher extent than with PAF-acether. Inhibition of the endotoxin-induced increase in PTLA was obtained with BN 52021, BN 52063 and dexamethasone, whereas aprotinin was ineffective. Since BN 52021 and BN 52063 reduced also the endotoxin-induced lethality in the rat, their antiprotease activity may be a consequence of their PAF-antagonistic effect. Further studies will be required with other PAF antagonists to assess fully this assumption.

Animals↗