Effect of iodinated water soluble contrast media on urinary protein assays.
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Contrast Media↗
Biomedical subjects
J Haylor
Publications and source records attributed to J Haylor.
Differential effect of L-nitroarginine methyl ester on urinary cGMP and kidney growth in the conscious rat following uninephrectomy.
The role of cGMP in compensatory renal growth (CRG) is uncertain, since inconsistent changes in renal cGMP have been reported following uninephrectomy (UNx) in the rat. The aim of this study was to reassess the change in cGMP following UNx in the conscious rat by sequential measurements of cGMP excretion and to determine the contribution of nitric oxide, an activator of guanylate cyclase, using L-NAME an inhibitor of nitric oxide synthase. In the conscious rat a sustained increase in the urinary excretion of cGMP was produced in the 7-day period following UNx. L-NAME (20 mg/kg per day) prevented the increase in cGMP excretion following UNx, but not compensatory renal growth. Total kidney DNA, however, was reduced by L-NAME. These observations dissociate the increase in cGMP after UNx from the process of renal hypertrophy.
Animals↗
Effect of diatrizoate on the function of the isolated perfused rat kidney.
The mechanism of the nephrotoxicity of water-soluble contrast media (WSCM) remains ill defined. We have studied the effect of diatrizoate on the isolated perfused rat kidney (IPRK). Emphasis was on the effect of low- and high-dose diatrizoate on glomerular filtration rate (GFR), renal perfusate flow (RPF), fractional excretion of albumin (FE Alb) and fractional reabsorption of sodium (FR Na). The addition of diatrizoate to the IPRK led to a dose-dependent biphasic change in RPF and GFR characterized by an initial transient increase followed by a marked and sustained decrease. Diatrizoate induced a diuresis and a parallel increase in urinary sodium excretion (fall of FR Na). Fe Alb was also increased in kidneys exposed to diatrizoate. Electron microscopy of a control kidney showed preservation of cellular architecture, which contrasted with the observed cytoplasmic vacuolation of proximal tubular cells after perfusion with diatrizoate. This study confirms a direct effect of WSCM on the function of the IPRK. In this experimental model, diatrizoate reproduces the effects observed in vivo on GFR and renal perfusion.
Animals↗
Involvement of renal autacoids in the direct effects of mixed amino acids on the kidney.
A pharmacological approach has been employed to investigate the involvement of renal autacoids in the direct effect of amino acids on the isolated rat kidney. The increase in renal perfusate flow induced by 6 mM mixed amino acids was inhibited by sulpiride, a dopamine antagonist. The change in GFR induced by 6 mM mixed amino acids was abolished by L-nitro-arginine methyl ester, an inhibitor of nitric oxide biosynthesis and partially inhibited by either sulpiride or indomethacin. It is concluded that several autacoids may mediate the direct effect of amino acids on the kidney with dopamine being primarily involved in hyperperfusion and nitric oxide involved primarily in hyperfiltration.
Amino Acids↗
Nitric oxide synthesis inhibitor prevents vasodilation by insulin-like growth factor I.
The effect of insulin-like growth factor I (IGF-I) on renal blood flow was measured in the anaesthetized rat using an electromagnetic flow probe. Renal vasodilation induced by IGF-I (50 micrograms/kg) was completely inhibited by NG-nitro-l-arginine methyl ester (50 mg/kg), an inhibitor of nitric oxide biosynthesis, but only partially reduced by indomethacin (10 mg/kg). The involvement of nitric oxide synthesis in the renal actions of IGF-I is proposed.
Animals↗
Renal sensitivity to endothelium-derived-relaxing-factor-mediated vasodilatation in the spontaneously hypertensive rat.
1. The sensitivity of the kidney to endothelium-derived-relaxing-factor-mediated vasodilatation has been investigated in the spontaneously hypertensive rat and the Wistar-Kyoto normotensive rat using an isolated perfused rat kidney model. 2. No difference in the slope, ED50 or maximum of the concentration-response curves for the endothelial-dependent vasodilators A23187, a calcium ionophore, and acetylcholine could be demonstrated between kidneys obtained from the spontaneously hypertensive and the Wistar-Kyoto normotensive rats. 3. No difference in the slope or the ED50 of the concentration-response curve for the endothelial-independent vasodilators, atrial natriuretic factor and sodium nitroprusside, could be demonstrated between kidneys obtained from the spontaneously hypertensive and the Wistar-Kyoto normotensive rats. However, in the spontaneously hypertensive rats, the maximum vasodilator response to atrial natriuretic factor, but not to sodium nitroprusside, was increased. 4. The perfused kidney from the spontaneously hypertensive rat also showed an increase in the maximum but not in the slope or ED50 of the concentration-response curve for vasoconstriction induced by the alpha 1-adrenoceptor agonist methoxamine. 5. The involvement of endothelium-derived relaxing factor in mediating the renal vasodilator response to A23187 and acetylcholine was confirmed in experiments performed in perfused kidneys obtained from normotensive Wistar rats. 6. It is concluded that the sensitivity of the kidney to endothelium-derived-relaxing-factor-mediated vasodilatation is not modified in the spontaneously hypertensive rat. This does not, however, exclude a role for the synthesis of endothelium-derived relaxing factor in the maintenance of blood pressure in the spontaneously hypertensive rat.
Acetylcholine↗
Mediators of the direct effects of amino acids on the rat kidney.
1. The response of the isolated rat kidney to a mixed amino acid solution was examined in the presence of three renal autacoid inhibitors, indomethacin (a cyclo-oxygenase inhibitor), sulpiride (a dopamine antagonist) and L-nitroarginine methyl ester (an inhibitor of nitric oxide synthesis). 2. Increasing the concentration of the mixed amino acid solution perfusing the kidney from 2 to 8 mmol/l (n = 6) produced a sustained increase in renal perfusate flow (P less than 0.01) and reversed the time-dependent fall in [14C]inulin clearance (P less than 0.01) demonstrated in kidneys perfused with 2 mmol/l mixed amino acids alone. A significant increase in the fractional sodium reabsorption and decrease in the fractional albumin excretion was also observed. 3. Indomethacin (10(-4) mol/l, n = 6) produced partial (50%) inhibition of the effect of mixed amino acids on [14C]inulin clearance, but did not influence their ability to increase renal perfusate flow. 4. Sulpiride (0.7 mumol min-1 kg-1, n = 6) produced partial inhibition of the effect of mixed amino acids on both [14C]inulin clearance and renal perfusate flow by 60% and 50%, respectively. Sulpiride also entirely inhibited the reduction in fractional albumin excretion. 5. L-Nitroarginine methyl ester (10(-4) mol/l, n = 6) completely inhibited the effect of mixed amino acids on [14C]inulin clearance, but did not inhibit the increase in renal perfusate flow, even though the basal vascular resistance was markedly enhanced. L-Nitroarginine methyl ester also inhibited the increase in fractional sodium reabsorption produced by the mixed amino acids. 6. It is concluded that prostaglandins, dopamine and nitric oxide may all have a role to play in the direct effect of mixed amino acids on renal function. This does not, however, preclude further modification by additional stimuli generated in vivo.
Albumins↗
Effect of probenecid on the urinary excretion of TXB2 and PGE2 in the anaesthetised rat.
In the anaesthetised rat, probenecid (33 mg/kg) produced a 50% fall in urinary TXB2 excretion indicating that a component of the TXB2 excreted in the urine is secreted by the proximal tubule. At a higher dose of probenecid (100 mg/kg) this effect was overcome, a relative increase in urinary TXB2 excretion being produced. This may provide evidence for the proximal reabsorption or bi-directional transport of TXB2 in the rat. At 100 mg/kg probenecid also produced an 8-fold increase in urinary PGE2 excretion. Although the bi-directional transport of PGE2 is well known, this is the first time urinary PGE2 excretion rate has been shown to be modified by probenecid. The increase in PGE2 excretion could obscure the assessment of any inhibition by probenecid of proximal PGE2 secretion. It could also provide evidence for the proximal reabsorption of PGE2. However the interpretation of probenecid-induced changes in eicosanoid excretion in terms of modified tubular reabsorption must be treated with caution since urinary eicosanoid excretion could be increased by other properties of probenecid including inhibition of either protein binding or the uptake of eicosanoids into the lung.
Animals↗
Urinary prostaglandin F2 alpha excretion is not pH-dependent in the conscious rat: implications for the urinary prostaglandin E2/prostaglandin F2 alpha ratio.
1. The influence of urine pH on the urinary excretion of prostaglandin (PG) F2 alpha and the PGE2/PGF2 alpha ratio has been examined in the conscious rat. 2. The basal urinary PGF2 alpha excretion rate of 3.9 pmol/h (n = 23) did not vary with urine pH. In marked contrast, PGE2 excretion increased as the urine became more alkaline. The PGE2/PGF2 alpha ratio therefore progressively increased from 1.5 to 22 as the pH of the urine changed from pH 5.8 to pH 7.8. 3. The independence of PGF2 alpha excretion from urine pH: (a) excludes cyclo-oxygenase as a potential site of action for the pH-dependence of urinary PGE2 excretion; (b) suggests that the urinary PGE2/PGF2 alpha ratio measured in alkaline urine may be a more accurate reflection of the kidneys, ability to synthesize these two prostaglandins in vivo; (c) suggests that control of urine pH is required before the urinary PGE2/PGF2 alpha ratio can be employed as an index of PGE2 9-ketoreductase (EC 1.1.1.189) activity in vivo.
Animals↗
Differential effects of amino acids on the isolated perfused rat kidney.
1. The direct effects of individual amino acids, including glycine (a neutral amino acid), L-glutamic acid (an acidic amino acid), L-leucine (a neutral, branched-chain amino acid) and L-arginine (a basic amino acid), on renal function were compared with a mixed amino acid solution by using the isolated rat kidney perfused with a physiological saline solution containing 6.7% (w/v) albumin and a basal level of 2 mmol/l mixed amino acids. 2. In a control series, the renal perfusate flow was stable but the glomerular filtration rate, as measured by [14C]inulin clearance, declined with time. A stable glomerular filtration rate could be obtained by increasing the basal perfusate amino acid concentration to 14 mmol/l. 3. The addition of 6 mmol/l mixed amino acids produced a sustained increase in renal perfusate flow and an increase in [14C]inulin clearance, reversing its time-dependent fall. Sodium reabsorption was enhanced, but, unlike the control series, no increase in fractional albumin excretion was obtained. 4. Renal perfusate flow was increased by glycine (6 mmol/l), L-arginine hydrochloride (6 mmol/l) and sodium glutamate (6 mmol/l) but remained unaffected by L-leucine. The vasodilatation induced by L-arginine hydrochloride and sodium glutamate was not sustained. 5. The time-dependent fall in [14C]inulin clearance was prevented by glycine, L-arginine and glutamic acid, but not by L-leucine. L-Arginine hydrochloride, like the mixed amino acid solution, produced a significant increase in [14C]inulin clearance.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acids↗
Cyclic GMP release and vasodilatation induced by EDRF and atrial natriuretic factor in the isolated perfused kidney of the rat.
1. Guanosine 3':5'-cyclic monophosphate (cyclic GMP) release and vascular tone was measured in the isolated kidney of the rat perfused at constant flow with Krebs-Henseleit solution. The effects of 3 vasodilators, acetylcholine (ACh), atrial natriuretic factor (ANF) and sodium nitroprusside (SNP) on the renal release of cyclic GMP and vascular tone were examined. The ability of the endothelial-derived relaxing factor (EDRF) inhibitors, haemoglobin and gossypol, to modify vasodilatation and vasodilator-induced changes in cyclic GMP releases from the kidney was also investigated. 2. Renal cyclic GMP release was elevated 8 fold by ANF (0.01 microM), 5 fold by SNP (1 microM) and 3 fold by ACh (0.3 microM). 3. For ACh, both the increase in renal cyclic GMP release and the vasodilatation were reduced by the EDRF inhibitors, haemoglobin (1 microM) and gossypol (15 microM). For SNP, neither the increase in renal cyclic GMP release nor vasodilatation were inhibited by gossypol (15 microM). 4. For ANF, neither the increase in cyclic GMP release from the kidney nor its vasodilator activity were affected by haemoglobin (1 microM). 5. EDRF inhibitors reduced the basal release of cyclic GMP from 0.32 +/- 0.06 pmol min-1 to 0.18 +/- 0.03 pmol min-1, gossypol being more effective than haemoglobin. 6. The results are consistent with the ability of ACh to induce EDRF-mediated vasodilatation in the isolated perfused kidney of the rat. Basal EDRF release appears to contribute approximately 50% to the basal release of cyclic GMP from this preparation. The renal vasodilator action of ANF however, is independent of EDRF, although the renal vascular endothelium cannot be discounted as a site at which ANF stimulates cyclic GMP production.
Acetylcholine↗
Vasopressin release in response to intravenously injected contrast media.
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Animals↗
Eicosanoids in renal function.
The major role of renal eicosanoid synthesis appears to be a protective one. In the cortex, prostaglandin synthesis minimises potential anoxic and ischaemic damage by vasodilatation. In the medulla, prostaglandin synthesis appears to stabilise the corticomedullary solute gradient and may play a role in cell volume regulation. Mono-oxygenase production at this site, by modifying blood flow and cellular active transport processes could again serve a protective function against anoxia and ischaemia. The release of erythropoietin also appears to be prostaglandin dependent. It is likely that leukotrienes released from inflammatory cells within the kidney will affect renal haemodynamics and capillary permeability as in other tissues.
Animals↗
Tubular mechanisms determining the urinary excretion of tritiated prostaglandin E2 in the anaesthetized rat.
1. The renal excretion of arterially injected tritiated prostaglandin E2 ([3H]PGE2) and its metabolites has been examined in the anaesthetized rat before and after the administration of probenecid (an inhibitor of proximal organic acid secretion). [14C]Inulin was employed as a freely filtered, non-reabsorbable marker, while [3H]p-aminohippurate was used to assess the inhibitory effect of probenecid. The experiments allowed us to quantify the tubular delivery, proximal secretion, intratubular metabolism, and tubular reabsorption of [3H]PGE2 by the whole kidney in vivo. 2. Following a single pass through the left kidney 25% of an injected dose of [3H]PGE2 was excreted, although only 1.7% of the injected 3H co-chromatogrammed with cold PGE2. The chemical content of PGE2 in the isotope employed, produced a slight but significant (P less than 0.05) fall (12%) in the single-pass excretion of [14C]inulin. 3. Intravenous probenecid (100 mg kg-1 + 100 mg kg-1 h-1) completely inhibited the proximal tubular secretion of [3H]p-aminohippurate, while the single-pass excretion of [14C]inulin remained unchanged. Probenecid also reduced the blood pressure and urine flow, and decreased the binding of [3H]PGE2 to plasma protein from 59 to 41%. 4. Probenecid administration reduced the single-pass excretion of 3H following an injection of [3H]PGE2 by 65% down to 8.5% of the injected dose. Due to the change in protein binding however, probenecid also increased the filtered load of [3H]PGE2 from 12 to 16% of the injected dose. 5. The following calculations were made concerning the tubular handling of [3H]PGE2 by the whole kidney in vivo. (i) Thirty-five per cent of the injected dose of [3H]PGE2 was secreted by the proximal tubules on a single pass through the kidney, in addition 12% was filtered while 59% was protein bound. (ii) The tubular reabsorption of [3H]PGE2 was 47% of the filtered load. (iii) [3H]PGE2 was subject to a high degree of intratubular metabolism which at a minimum value represented about 50% of the filtered load. The metabolism of [3H]PGE2 also occurred during proximal tubular secretion.
Animals↗
The effect of sodium bicarbonate on the flow-dependency of urinary prostaglandin excretion in man.
The influence of oral water loading on the excretion rate of prostaglandin (PG) E was investigated in healthy human subjects in a control study where the urine was acidic (pH 5.7) and after oral sodium bicarbonate, which made the urine mildly alkaline (pH 7.2). PGE was immediately extracted from urine and measured by a radioimmunoassay technique. After sodium bicarbonate (5 g) the urinary PGE excretion rate was some three-fold higher (P less than 0.01) than in the control study, in the absence of any significant difference in the urine flow (approximately 80 ml/h). In the control study (urine pH 5.7) the urinary PGE excretion rate increased significantly (P less than 0.01) as the urine flow rose in response to the oral fluid load. However, after sodium bicarbonate, PGE excretion did not alter after the fluid load despite a 10-fold increase in urine flow. Since after bicarbonate administration PGE excretion is independent of urine flow, mildly alkaline urine may represent a condition under which renal PGE synthesis can be effectively assessed from measurements of urinary PGE excretion, in the presence of changes in urine flow. In addition, the results are compatible with the hypothesis that, in man, PGE may be passively reabsorbed in the distal nephron, and a reduction in this reabsorption could contribute to or be responsible for the dependency of the excretion rate of PGE on urine flow.
Adult↗
Urine pH and the relationship between urine flow and urinary prostaglandin E excretion in the rat.
The relationship between urine flow and urinary prostaglandin E (PGE) excretion was investigated at constant urine pH in the anaesthetized rat. The urine pH was maintained at approximately pH 6 or pH 8 by the intravenous infusion of either ammonium chloride or sodium bicarbonate respectively. Two distinct patterns in the relationship between PGE excretion and urine flow were observed. The first showed a fall in urinary PGE excretion as the urine flow increased over the low flow range of 2-5 ml/h, and was common to both experiments. The second relationship, however, showed a marked difference between the ammonium chloride and sodium bicarbonate experiments since: (a) in acidic urine (pH 6), PGE excretion increased (P less than 0.002) with the urine flow, attaining a rate of 87 +/- 6 pmol/h (n = 6) at the highest level of flow achieved (12 ml/h); (b) in alkaline urine (pH 8), PGE excretion was significantly (P less than 0.01) higher but did not increase with urine flow, remaining constant at approximately 90 pmol/h (n = 6). The lack of any additive effect on urinary PGE excretion between increasing the urine flow and making the urine alkaline may be explained by both stimuli acting through a common mechanism, a concept which is consistent with the hypothesis that PGE may be reabsorbed in the distal nephron. The flow-dependency of urinary PGE excretion could therefore result from a reduction in reabsorption rather than the increase in passive secretion proposed previously.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Is the urinary excretion of prostaglandin E in man dependent on urine pH?
The relationship between urine pH, modified by the oral administration of either ammonium chloride or sodium bicarbonate, and the urinary excretion of prostaglandin E (PGE) was studied in healthy female subjects. The urinary concentration of PGE, normally constant in man, was significantly higher (P less than 0.02) in alkaline than in acid urine. pH-dependent metabolism and flow-dependent excretion were identified as two factors liable to obscure the demonstration of the pH-dependency of the urinary excretion rate of PGE in man.
Adult↗
The effect of urine pH on the reduction of urinary PGE2 excretion by indomethacin.
Urinary PGE2 excretion is influenced by urinary pH, being higher at high pH values. Indomethacin (10 mg/kg body wt, i.p.) was found to reduce urinary PGE2 excretion to the same absolute value irrespective of the initial PGE2 output. It is concluded that measurements of 'percentage inhibition' of urinary PGE2 excretion by non-steroidal anti-inflammatory agents must be interpreted with caution.
Animals↗