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J L Ader

Publications and source records attributed to J L Ader.

At least 37 records · Page 2Linked to original sources
PubMed1995

In vivo and in vitro homologous desensitization of rat glomerular bradykinin B2 receptors.

We investigated the effects of bradykinin on glomerular bradykinin B2 receptor functions and parameters in vivo, after intrarenal infusion of bradykinin, and in vitro, after incubation of isolated rat glomeruli with bradykinin. Bradykinin transiently increased renal plasma flow whereas a second challenge was ineffective. Scatchard analysis demonstrated the presence of two populations of bradykinin binding sites whose densities were similarly decreased by about 40% after intrarenal bradykinin infusion. This decrease was not altered by an acid wash suggesting internalization of the radiolabelled ligand. The effect of bradykinin was prevented by a bradykinin B2 receptor antagonist. Pre-exposure of isolated rat glomeruli to bradykinin mimicked the in vivo results because there was a reduction in bradykinin-induced prostaglandin E2 and prostaglandin F2 alpha release. Rapid recovery was observed 15 min after washing out the bradykinin. Our results directly demonstrate a negative homologous down-regulation of B2 glomerular bradykinin receptor density under both in vivo and in vitro conditions, an effect which involves a rapid sequestration of the receptor.

Animals↗
PubMed1995

Renal functional reserve in calcium channel blocker-treated hypertensive recipients of kidney transplant.

Renal functional reserve during infusion of an amino acid solution was examined in 12 cyclosporin-treated kidney recipients at 1 (T1) and 8 months (T2) after transplantation. Patients were retrospectively divided into six normotensive (NT) and six hypertensive recipients (HT) maintained on monotherapy with a calcium channel blocker. Baseline glomerular filtration rates (GFR) were similar in NT and HT at T1 and T2. Renal functional reserve was identical in NT and HT at T1 (15 +/- 7 vs 18 +/- 13 ml/min/1.73 m2) but significantly greater in HT at T2 (11 +/- 5 vs 23 +/- 10 ml/min/1.73 m2; P < 0.05). At T2, baseline proximal tubule outflow (lithium clearance) was greater in HT (26 +/- 8 vs 16 +/- 3 ml/min/1.73 m2; P < 0.05), whereas fractional proximal reabsorption was less (54 +/- 11% vs 67 +/- 5%; P < 0.05). These results indicate that: (i) hypertensive recipients on calcium channel blocker therapy do not exhibit permanent glomerular hyperfiltration until 8 months after transplantation, and have a reduced proximal reabsorption; (ii) measurement of amino acid-stimulated GFR and renal functional reserve is a more sensitive method than that of baseline GFR for evaluating renal function and the effects of therapy in kidney recipients.

Adult↗
PubMed1994

Renal functional reserve in cyclosporin-treated recipients of kidney transplant.

The aims of this study were to determine whether renal functional reserve (RFR) is still present in cyclosporin-treated renal transplant recipients, and to examine the relationship between RFR and proximal reabsorption. A serial study was carried out in 12 renal allograft recipients (R) with good renal graft function at 20 +/- 2.5 days (S1) and at 7.6 +/- 0.4 months (S2) post-transplantation, and the results were compared to those in eight subjects who had undergone unine-phrectomy (one-kidney controls: UNx.C) and in 12 healthy volunteers (two-kidney controls: 2K.C). R and C were in similar sodium and protein balance and with similar plasma renin and aldosterone levels. R had normal serum creatinine level on moderate doses of cyclosporin (whole blood cyclosporin concentration: 212 +/- 20 and 125 +/- 20 ng/ml at S1 and S2, respectively). Eight one-hour clearance periods were performed prior to, during and following a three-hour i.v. infusion of a mixture of 20 l-amino acids (Azonutril 25, 4.5 mg amino acids/kg/min). Baseline glomerular filtration rate (GFR) was lower in recipients at S1 and S2 (55 +/- 5 and 54 +/- 4 ml/min/1.73 m2, respectively) than in UNx.C and 2K.C (72 +/- 4 and 113 +/- 4 ml/min/1.73 m2, respectively, P < 0.05 and 0.001). Amino acid infusion elicited significant GFR increases in controls as well as in recipients in spite of higher renal vascular resistances (RVR). The greater measured increase in GFR, which represented RFR, was 18 +/- 3 and 28 +/- 2 ml/min/1.73 m2 in UNx.C and 2K.C, respectively (P < 0.001), and 17 +/- 3 ml/min/1.73 m2 in R at both S1 and S2 (P < 0.001). Contrary to both UNx and 2K controls, the acute hyperfiltration in R at S1 and S2 occurred with a significant increase in effective renal plasma flow, no alteration in filtration fraction and a large decrease (approximately 20 and 17%) in RVR while no correlation could be detected between the RFR and baseline GFR. Baseline lithium clearance, used as a marker of overall proximal fluid delivery (CLi), was significantly lower, whereas baseline fractional excretion of lithium (FELi) was significantly higher in R at S1 and S2 and in UNx.C (41 +/- 4, 40 +/- 3 and 38 +/- 3%, respectively) than in 2K.C (31 +/- 2%, P < 0.05). Consistent and significant increase in CLi, FELi and absolute proximal reabsorption occurred both in R at S1 and S2 and in UNx and 2K controls during elicitation of RFR.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

Skeletal manifestations of moderate phosphate diabetes.

Six patients, with vertebral osteoporosis and reflex sympathetic algodystrophy syndrome of the lower limbs, due to moderate diabetes, are presented. Osteoporosis was documented by low CT scan bone density and moderate decrease of bone trabecular volume. Histomorphometric studies found a mild increase of resorption areas. All patients had unremarkable serum phosphorus level (mean: 0.91 +/- 0.13) but increase of urinary phosphorus excretion was documented by phosphate clearance higher than 20ml/mm, phosphate tubular reabsorption lower than 80% and TmPo4/GFR lower than 0.8mmol/l. Phosphate clearance and phosphate tubular reabsorption are studied in two control groups. Mild phosphate diabetes, of unknown incidence and prevalence (need for prospective studies) may be the vector of osteoporosis, vertebral and peripheral. The diagnosis of PD requires determination of phosphate clearance, phosphate tubular reabsorption, TmPo4/GFR and these tests may be useful in the diagnostic work up of bone demineralization disorders. We thought that osteoporosis could be the result of progressive dissolution of bone apatite crystals necessary to maintain normal or sub-normal blood phosphate level in spite of the phosphate diabetes.

Adult↗
PubMed1992

Direct effects of bradykinin on glomerular filtration and proximal tubule reabsorption in rat kidney.

Intrarenal infusion of a low dose of bradykinin devoid of extrarenal action exerts direct vasodilator and diuretic effects on rat kidney. It does not significantly alter glomerular filtration rate and absolute proximal reabsorption but increases the delivery of fluid from the proximal tubule evaluated by the clearance of lithium. None of these effects are observed in kidneys infused with both bradykinin and a specific bradykinin antagonist.

Animals↗
PubMed1992

[Male osteoporosis, an unrecognised etiology: moderate idiopathic proximal tubulopathy (MIPT)].

Routine renal tubular investigations in 8 osteoporotic men, in whom phosphorus/calcium balance studies were normal or almost normal revealed moderate phosphorus (PD) or bicarbonate (BD) diabetes possibly responsible for their decalcification. Osteoporosis affected the spine and lower limbs, resulting in clinical pictures of frequently recurrent spontaneous algodystrophy. Histomorphometric studies revealed an increase in surface areas of resorption, the diagnosis of PD being based upon the finding at several successive investigations, in the absence of any drug treatment, of a phosphorus clearance of greater than 20 ml/min and/or a phosphorus reabsorption level of less than 80%. Arterial HC03 levels of greater than 21 mEg/l and a fractional bicarbonate excretion (FBE) of greater than 15% enabled the diagnosis of bicarbonate diabetes (proximal tubular acidosis). These cases of PD and BD appeared to be secondary to proximal tubulopathies for which no known etiology was found.

Acidosis, Renal Tubular↗
PubMed1991

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↗
PubMed1991

Phosphate diabetes associated with bone metastases of oat cell lung cancer.

Although the link between phosphate diabetes and neoplasm or benign mesenchymal tumors has been well documented, the nature of the phosphaturia factor remains unknown. We describe two cases of phosphate diabetes associated with bronchogenic cancer. In these case reports, we suggest that fibroblasts or osteoblasts synthesize a phosphate eliminating substance.

Aged↗
PubMed1990

Effects of chronic administration of an angiotensin-converting enzyme inhibitor on angiotensin-converting enzyme activity in the pars recta of rabbits.

1. To determine whether chronic angiotensin-converting enzyme inhibition induces a decrease in proximal tubular angiotensin-converting enzyme activity, urine and blood samples were collected in conscious New Zealand rabbits before and after 16 days administration in drinking water of low doses of captopril (2.6 +/- 0.6 mg 24 h-1 kg-1), high doses of captopril (7.6 +/- 0.9 mg 24 h-1 kg-1) or no captopril (controls). The kidneys were then removed and angiotensin-converting enzyme activity was determined in isolated pars recta of microdissected nephrons as pmol of tritiated hippurylglycylglycine substrate hydrolysed min-1 of incubation and mm-1 of tubule. 2. Both low and high doses of captopril significantly decreased plasma angiotensin-converting enzyme activity and increased plasma renin activity, thus indicating an effective inhibition of circulating angiotensin-converting enzyme. Both low and high doses of captopril also significantly decreased mean arterial pressure and increased water intake and urine flow rate. Neither dose modified creatinine clearance and absolute and fractional sodium excretion. 3. None of the doses altered urinary kallikrein excretion. Urinary excretion of kinins was increased by 98.7% compared with control rabbits by the high dose of captopril (402 +/- 152 vs 251 +/- 104 ng/24 h, P less than 0.01) but was unchanged by the low dose of captopril. 4. Angiotensin-converting enzyme activity in the pars recta was lower in rabbits given the high dose of captopril than in control rabbits (17.6 +/- 7.2 vs 37.3 +/- 9.0 pmol min-1 mm-1, P less than 0.01) but was not decreased in rabbits given the low dose of captopril (40.4 +/- 5.0 pmol min-1 mm-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Nephron sites of the natriuretic effect of intrarenal infusion of atrial natriuretic peptide in the rat.

Since renal mechanisms by which ANP induces a natriuresis remain unclear, the effects of the infusion of 0.03 micrograms/min/kg body weight of rANP 1-28 into the right renal artery (via a very thin catheter inserted into the suprarenal artery) were studied in anesthetized rats using lithium clearance to monitor proximal tubular function. Intrarenal ANP did not cause changes in arterial pressure and hematocrit, nor in contralateral kidney handling of sodium. Its natriuretic effect on the right kidney resulted from an increase in the filtered load of sodium and from a decrease in reabsorption in the distal segments of the nephron. Proximal tubule sodium reabsorption increased in proportion to the filtered load.

Animals↗
PubMed1989

Renal kallikrein activity in rats developing spontaneous hypertension.

1. Spontaneously hypertensive rats (SHR) excrete less kallikrein in urine than Wistar-Kyoto rats (WKY) during the developmental phase of hypertension. The present study was designed to examine whether the urinary defect is related to abnormalities in the renal kallikrein content in this hypertensive model. 2. Active and total kallikrein were measured (amidolytic assay) in the renal cortex of newborn and 4-, 8- and 12-week-old SHR and age-matched WKY. Active and total kallikrein were also measured in urine at the same ages, except at birth. 3. Tissue active kallikrein was significantly lower in SHR at birth, representing on average 53% of the values in WKY expressed as content per total cortex weight. Tissue total kallikrein did not differ between newborn SHR and WKY. 4. SHR at 4, 8 and 12 weeks of age had lower urinary active and total kallikrein excretion. Tissue active akllikrein, but not total kallikrein, was higher than in age-matched WKY per g of cortex weight or per mg of protein, whereas both tissue active and total kallikrein were lower in SHR when expressed as content per total cortex weight. At these three ages, active kallikrein represented, on average 86%, while total kallikrein represented 77%, of the values in age-matched WKY. 5. Our results indicate a defect in prokallikrein activation rather than in kallikrein synthesis in the renal cortex of SHR at birth. The reduction in urinary kallikrein excretion during the developmental phase of hypertension in young SHR is similar to the reduction observed in the renal tissue.

Aging↗
PubMed1988

Renal tissue kallikrein in newborn and young SHR.

Since young SHR excrete less urinary kallikrein than WKY, active and total kallikrein (A and T Kall, respectively) was measured (amidolytic assay) in the renal cortex of both strains. Neither at birth nor at age 4 weeks did renal T Kall differ between SHR and WKY. Renal A Kall was significantly lower in newborn SHR and higher in 4-week-old-SHR than in age-matched WKY. Our results indicate that urinary kallikrein does not accurately reflect the renal enzyme activity. They suggest that SHR exhibit an inherited defect in prokallikrein activation and a secondary defect in the release of tissue kallikrein into urine.

Aging↗