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C Emond

Publications and source records attributed to C Emond.

26 records · Page 2Linked to original sources

Glomerular B2-kinin-binding sites in two-kidney, one-clip hypertensive rats.

To extend our recent observations of the possible downregulation of glomerular B2-kinin-binding sites, we investigated density (Bmax) of bradykinin (BK)-binding sites in glomerular membranes of both the clipped (C) and nonclipped (NC) kidneys of two-kidney, one-clip (2K-1C) Goldblatt hypertensive rats, in relation to tissue kallikrein activity and glomerular three-dimensional structure. Compared with the Bmax of sham-operated (SO) kidney (31.8 +/- 7 fmol/mg protein), a significant increase in Bmax was observed in glomeruli of both kidneys in hypertensive rats, the Bmax being higher in glomeruli of NC than in C kidneys (98 +/- 11 vs. 59 +/- 12 fmol/mg protein). NC kidney compensatory hypertrophy was expressed by an increase in glomerular diameter, surface area, and volume. When expressed per unit of area or volume, Bmax in NC kidneys remained significantly higher than in both C and SO kidneys. Increased Bmax in both kidneys of 2K-1C rats was associated with a decreased intrarenal level of kallikrein. We also examined prostaglandin (PG) E2 release by isolated glomeruli from SO, C, and NC kidneys as a possible biological effect induced by BK. Whereas C kidney released more PGE2 than NC kidney under basal conditions, addition of BK (10 nM) induced greater PGE2 production in NC kidney consistent with the difference in Bmax between C and NC kidneys. These results suggest a possible downregulation of glomerular B2-binding sites by bradykinin, which may explain the difference between SO and C kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Characterization of a B2-bradykinin receptor in rat renal mesangial cells.

The specific binding of bradykinin (BK) was investigated using membrane fractions from mesangial cells in primary culture, a cloned cell line, and in intact adherent cells with three different radiolabelled BK analogues: 125I-[Tyr0]BK, 125I-[Tyr5]BK and 125I-[Tyr8]BK. The best radioligand was 125I-[Tyr0]BK, and assay conditions were determined to ensure maximal stable binding. Binding appeared to be reversible and not to be inhibited by a wide variety of protease inhibitors including converting enzyme inhibitor and phosphoramidon. The maximum density of binding sites (Bmax) was about 88 +/- 18 fmol/mg protein, which is equivalent to about 6000 sites/cell, and the dissociation constant averaged 2 nM. No significant difference in Bmax was observed between membranes from cells in primary culture and those from cloned cells. Of the BK analogues tested, unmodified BK exhibited the highest inhibition constant (close to 10(-10) M). No displacement of 125I-[Tyr0]BK was observed in the presence of the B1 agonist des-Arg9-BK or several unrelated peptides, including atrial natriuretic factor and angiotensin I and II, whereas 50% inhibition of binding was achieved with the B2 antagonist [D-Arg,Hyp3,D-Phe7]BK (10(-9)M). Addition of BK for 3 min to the incubation medium of cloned mesangial cells induced a dose- and time-dependent increase in PGE2 unlike des-Arg9-BK, which showed no such effect. The secretion was strongly inhibited by prior incubation with the B2 antagonist [D-Arg,Hyp3,D-Phe7]BK. The pharmacological profile of the binding site determined with various BK agonists and antagonists, and the stimulating effect of binding site activation on prostaglandin release strongly suggest that B2-kinin-like receptors are present in rat mesangial cells.

Animals↗

[Use of salbutamol in the treatment of severe hyperkalemia in hemodialysed patients].

The possibility of obtaining a rapid fall of kalaemia in patients with renal failure under haemodialysis by injecting salbutamol intravenously in doses of 0.5 mg over 15 minutes was tested in 11 subjects. Kalaemia fell by 1.08 +/- 0.30 mmol in 30 minutes, 75 per cent of the effect being obtained at the end of the infusion. Malaise with tachycardia was frequent but always transient. Thus, a rapid infusion of salbutamol seems to be well tolerated and effective against hyperkalaemia, provided two contra-indications are observed: coronary disease and treatment with beta-blockers.

Albuterol↗

Effect of changes in sodium or water intake on glomerular B2-kinin-binding sites.

In a previous study, we characterized a B2-kinin-binding site in rat glomerular membranes. We have now investigated the density and affinity of this binding site for bradykinin (BK) in rat glomerular membranes, in relation to the renal and urinary levels of kallikrein during changes in sodium and water intake. The density of BK-binding sites was reduced after 28 days of low-sodium diet (12.5 +/- 1.3 vs. control: 32.1 +/- 5.2 fmol/mg protein, P less than 0.05), whereas the concentration and activity of kallikrein was increased in the renal tissue and in the urine. Water deprivation for 4 days also resulted in a decreased density of binding sites (13.2 +/- 1.2 vs. control 32.1 +/- 5.2 fmol/mg protein, P less than 0.05) and, interestingly, renal kallikrein levels increased. During high salt consumption, urinary kallikrein activity increased but the renal concentration and activity of kallikrein was unchanged. In this high-sodium-loaded group, BK-binding site density was similar to controls receiving a normal-sodium diet (41.6 +/- 8.4 vs. control 32.1 +/- 5.2 fmol/mg protein). On the other hand, the binding affinity of BK did not change significantly in all experimental groups, and the binding specificity was not altered as BK remained the most potent agonist. Sodium depletion and water deprivation led to the same effects on BK-binding sites and on renal kallikrein. The renal glomerular BK-binding site density decreased in both conditions, whereas the renal level of kallikrein was enhanced. An inverse relationship between renal kinin levels and the density of glomerular BK-binding sites is therefore suggested.

Animals↗

[Evidence for a glomerular receptor for bradykinin in rats. Effect of sodium intake on density and affinity of the receptor].

Bradykinin (BK) have been involved in a lot of pharmacological and biological effects including natriuresis, vasodilatation, inflammation and pain mediation. All these potent effects of BK are presumably mediated via one or more specific receptors which have been classified in two types named B1 and B2 receptors. In the kidney, specific binding have been reported successively in cortical epithelial membranes, in renomedullary interstitial cells and in cortical collecting tubules. Furthermore, since a large number of vasoactive compounds have been shown to regulate renal glomerular hemodynamics, we examined the binding of BK in rat glomerular membranes and the effect of variable salt diet on the density (Bmax) and the dissociation constant (KD) of this binding. Incubation of a radiolabeled bradykinin analog, [125I]-Tyr8-BK with a crude membrane preparation obtained from isolated rat glomeruli revealed a time dependent binding. The binding was saturable, reversible and was a linear function of protein membrane concentration. The radiolabeled Tyr8-BK bound to a single class of binding sites with an equilibrium dissociation constant (KD) of 2.75 +/- 0.7 nM and a density (Bmax) of 32.1 +/- 5.2 fmol/mg protein. [125I]-Tyr8-BK binding was reversed by bradykinin (Ki = 0.4 10(-9) M) and by other kinin analogs. However, Des-Arg9-BK had no effect on binding of the radiolabelled BK. These results are consistent with the presence of a B2-kinin like receptor in rat glomeruli. Low salt diet (during one month) and water deprivation (during 4 days) induced a decrease in the density of glomerular BK like receptors respectively (Bmax = 12.45 +/- 1.3 and 13.25 +/- 1.17 fmol/mg protein).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Middle molecule accumulation in uremia: an "extra uremic factor".

To evaluate middle molecule (MM) accumulation in relation with patients' well-being, plasma MM were analyzed in 115 uremic patients by using the two-step chromatographic technique described by Fürst et al. Unexpectedly, most of the patients exhibited small or undetectable subpeaks 7a, 7b, 7c, 7d. However, patients on regular dialysis treatment tend to present higher MM concentrations when a complication, such as infection, hyperparathyroidism, symptomatic neuropathy, or intercurrent disease occurs and peak 7d was very prominent after radio-contrast media administration. No correlation was found between plasma MM and small molecule accumulation (urea, creatinine, and uric acid) or residual renal function or hematocrit. An unexpected correlation was found between some MM fractions and serum PTH. These results indicate that MM do not accumulate in plasma only as a result of impaired renal function. This suggests considerable variations in their generation rates may be due to unknown misleading artifacts, PTH breakdown products, or other factors.

Adolescent↗