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Biomedical subjects

J Haylor

Publications and source records attributed to J Haylor.

At least 19 recordsLinked to original sources
PubMed1998

The haemodynamic effects of iodinated water soluble radiographic contrast media: a review.

All classes of iodinated water-soluble radiographic contrast media (RCM) are vasoactive with the iso-osmolar dimers inducing the least changes in the vascular tone. The mechanisms responsible for RCM-induced changes in the vascular tone are not fully understood and could be multifactorial. A direct effect on the vascular smooth muscle cells causing alterations in the ion exchanges across the cell membrane is thought to be an important factor in RCM-induced vasodilatation. The release of the endogenous vasoactive mediators adenosine and endothelin may also play a crucial role in the haemodynamic effects of RCM particularly in the kidney. In addition, the effects of RCM on blood rheology can cause a reduction in the blood flow in the microcirculation. The purpose of this review is to discuss the pathophysiology of the haemodynamic effects of RCM and to offer some insight into the biology of the endothelium and vascular smooth muscle cells as well as the pharmacology of the important vasoactive mediators endothelin and adenosine.

Adenosine↗
PubMed1997

Effect of radiographic contrast media on endothelium derived nitric oxide-dependent renal vasodilatation.

The effect of diatrizoate (Urografin325) on the cumulative dose-response curve of the vasodilatory response to acetylcholine was studied in the isolated perfused rat kidney (IPRK). The effect of 1-nitroarginine methyl ester (L-NAME) (10 mumol l-1) on the cumulative concentration-response curve of the vasodilatory response to acetylcholine and sodium nitroprusside was also studied. Acetylcholine is a vasodilator dependent on nitric oxide (NO) synthesis by the endothelium; sodium nitroprusside is a vasodilator not dependent on endogenous NO synthesis and L-NAME is an inhibitor of endogenous NO synthesis. The effect of L-NAME (10 mumol l-1) on the vasodilatory effect of diatrizoate which is observed in the presence of endothelin A receptor antagonist (BQ123, 10 mumol l-1) was also studied. In all experiments an infusion of angiotensin II (5 ng min-1) was maintained to increase the vascular tone of the preparation. Acetylcholine induced vasodilatation and the maximum increase in renal perfusate flow (RPF) was 17.0 +/- 1.7%, (p < 0.05). Diatrizoate (20 mgl ml-1 perfusate concentration) which induced a sustained fall in the RPF (-31.0 +/- 1.7%, p < 0.05) had no effect on the vasodilatory response to acetylcholine, and a similar increase in the RPF (17.8 +/- 2.2%, p < 0.05) was observed. In contrast, L-NAME (10 mumol l-1) completely abolished the vasodilatory effect of acetylcholine and produced instead a modest decrease in RPF by -5.0 +/- 1.7% (p < 0.05). The vasodilatory effect of sodium nitroprusside was not affected by L-NAME, confirming its selectivity as an inhibitor of endogenous NO synthesis in the IPRK. The maximum increase in the RPF induced by sodium nitroprusside was 23.1 +/- 2.0% (p < 0.05) in the absence of L-NAME and 21.2 +/- 2.2% (p < 0.05) in its presence. L-NAME did not interfere with the vasodilatation induced by diatrizoate in the presence of BQ123. In the presence of BQ123 alone the RPF increased from 23.3 +/- 1.4 ml min-1 g-1 to 26.5 +/- 1.0 ml min-1 g-1 (p < 0.05). In the presence of L-NAME and BQ123 the RPF increased from 24.4 +/- 3.0 ml min-1 g-1 to 27.2 +/- 2.7 ml min-1 g-1 (p < 0.05). There was no difference between the two groups (p > 0.05). In conclusion, diatrizoate did not interfere with endothelium derived NO-dependent vasodilatation in the kidney. A reduced production of NO in the vascular endothelium induced by contrast media is unlikely to play any role in the pathophysiology of the increase in renal vascular resistance produced by these agents. The renal vasodilatation induced by diatrizoate is not dependent on endogenous production of NO.

Acetylcholine↗
PubMed1996

Renal function and morphometry in the dwarf rat following a reduction in renal mass.

BACKGROUND: The compensatory increase in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) which follows a reduction in renal mass may be mediated by growth hormone, a renal vasodilator. METHODS: GFR, ERPF and glomerular morphometry were assessed in the dwarf rat, selectively deficient in GH, and compared its Lewis base strain. Studies were performed 21-days after sham-operation, unilateral nephrectomy or subtotal nephrectomy in age-matched animals. GFR and ERPF were assessed from the renal clearance of inulin and p-aminohippurate measured under barbiturate anaesthesia. RESULTS: The dwarf rat had a lower GFR and ERPF than the Lewis rat, in proportion to its lower body weight and lower kidney weight. Kidneys from the dwarf rat had a similar number of glomeruli to the Lewis, but smaller glomerular components in proportion to a lower kidney weight. Following unilateral nephrectomy, GFR (dwarf + 58%, Lewis + 53%) and ERPF (dwarf + 58%, Lewis + 52%) increased to a similar degree in both rat strains. Glomerular diameter, volume and capillary surface area increased in proportion to kidney growth, although compensatory renal growth (dwarf + 62%, Lewis + 78%) was somewhat lower in the dwarf. Following 5/6 subtotal nephrectomy, GFR (dwarf + 143%, Lewis + 171%) increased to a similar degree in both rat strains while ERPF (dwarf + 108%, Lewis + 48%) and compensatory renal growth (dwarf + 115%, Lewis + 86%) were greater in the dwarf than the Lewis rat. Subtotal nephrectomy was also associated with an increase in the thickness of the glomerular basement membrane in both rat strains. CONCLUSIONS: The results do not support a role for GH in the compensatory increase in renal function or hypertrophy which follows a reduction in renal mass, excluding this as a potential mechanism for GH-dependent renal scarring.

Animals↗
PubMed1995

Relationship between the diuretic effect of radiocontrast media and their ability to increase renal vascular resistance.

The relationship between diuresis and natriuresis induced by radiocontrast media (RCM) and their renal haemodynamic effects were investigated. The effects of the iso-osmolar iotrolan and the hyperosmolar diatrizoate on the renal vascular resistance (RVR) were studied in the filtering and non-filtering variants of the isolated perfused rat kidney (IPRK) preparation. In the non-filtering model, no tubular regulatory process can be activated. The effect of diatrizoate on the RVR of the filtering IPRK in the presence of fursemide (0.3 mmol l-1) an inhibitor of the tubuloglomerular feedback (TGF) was also investigated. There was no significant difference (p > 0.05) in the response of the filtering (n = 6) and non-filtering (n = 6) IPRK to iotrolan. The induced reduction in the renal perfusate flow (RPF) by iotrolan was 20.5 +/- 3.05% and 22.9 +/- 3.03%, respectively. The reduction in the RPF which was observed with diatrizoate in the non-filtering IPRK (n = 5, 17.5 +/- 3.04%) was significantly less (p < 0.05) in comparison to that of the filtering IPRK (n = 6, 26.9 +/- 4.28%). In the frusemide experiments, a reduction in the RPF comparable to that of the non-filtering kidney was observed (n = 5, 13.7 +/- 4.34%). This study demonstrates that the renal vascular effect of diatrizoate is partially dependent on the TGF response. No tubular regulatory mechanism was accountable for the haemodynamic effect of iotrolan. The activation of the tubular response is osmolarity dependent.

Animals↗
PubMed1994

Reduced depression of renal function by iotrolan in the isolated rat kidney.

The direct effects of iotrolan, a non-ionic dimer, on renal function were compared to iopromide, a non-ionic monomer and diatrizoate, an ionic monomer using the isolated perfused rat kidney. Kidneys were perfused ex vivo at 100 mmHg in a recirculating perfusion system with an albumin-based perfusate containing angiotensin II. All contrast media were studied at starting concentration of 20 mg Iodine/ml of renal perfusate. Each contrast agent produced a biphasic effect on the glomerular filtration rate (GFR) characterised by a transient increase followed by a sustained fall. However, the sustained fall in GFR induced by iotrolan (-24.7 +/- 2.1%) was significantly smaller than that produced by diatrizoate (-40.6 +/- 3.5%, P < 0.05) but there was no significant difference in comparison to the fall induced by iopromide (-34.2 +/- 3.7%). Each contrast agent produced a sustained decrease in renal perfusate flow (RPF) with iotrolan exerting a significantly smaller response (-21.7 +/- 2.0%) than either diatrizoate (-29.4 +/- 2.6%, P < 0.05) or iopromide (-32.2 +/- 2.9%, P < 0.05). The results indicate that at an equivalent iodine concentration iotrolan produces a smaller reduction of renal function in comparison to either iopromide or diatrizoate.

Animals↗
PubMed1994

Role for endothelin in the renal responses to radiocontrast media in the rat.

1. The involvement of endothelin in the renal responses to radiocontrast media was examined in the rat in vitro and in vivo using BQ123, a selective endothelin (ETA) receptor antagonist, and phosphoramidon, an endothelin-converting enzyme inhibitor. 2. For experiments in vitro, an isolated perfused rat kidney was employed perfusing in closed circuit with an albumin-based Krebs-Henseleit solution. The effects of BQ123 and phosphoramidon on the renal responses to iotrolan (iso-osmolar radiocontrast media) and diatrizoate (high-osmolar radiocontrast media) were examined. In vivo, renal conductance was measured using a Doppler flow probe in the anaesthetized rat pretreated with indomethacin, and the effects of BQ123 and phosphoramidon on the renal response to intravenous diatrizoate were examined. 3. In vitro, iotrolan and diatrizoate both produced a biphasic effect on the glomerular filtration rate, characterized by a transient increase followed by a sustained fall. Pretreatment with BQ123 (10 mumol/l), but not phosphoramidon (1 mmol/l), prevented both the increase and the sustained fall in glomerular filtration rate induced by radiocontrast media. 4. In vitro, iotrolan and diatrizoate both produced a sustained fall in renal perfusate flow. An initial increase in renal perfusate flow was only observed with diatrizoate. Pretreatment with BQ123 (10 mumol/l), but not with phosphoramidon (1 mmol/l), markedly inhibited the sustained fall in renal perfusate flow produced by both iotrolan and diatrizoate. BQ123 (10 mumol/l), however, markedly potentiated the renal vasodilatation produced by diatrizoate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗