Regulation Of Renal Blood Flow Research Articles

Ovariectomy enhances renal cortical expression and function of cyclooxygenase-2

Cyclooxygenase-2 (COX-2) inhibitors are used as analgesics in postmenopausal women, who develop edema and require a salt-restricted diet. This study was performed to determine the renal expression of COX-2 and on COX-2-dependent regulation of renal blood flow (RBF) in ovariectomized rats. Sprague-Dawley rats were divided into 4 groups: sham-operated rats fed a normal-salt diet (Sh+NS) or a low-salt diet (Sh+LS), and bilaterally ovariectomized rats fed a normal-salt diet (Ox+NS) or a low-salt diet (Ox+LS) (N= 6 in each group). Estrogen replacement therapy was performed on other ovariectomized rats. A renal clearance study was performed in anesthetized animals. Ovariectomy increased renal cortical COX-2 expression independently of dietary salt intake (Sh+NS <Ox+N; Sh+LS <Ox+LS). Inhibition of COX-2 by NS398 reduced the urinary excretion of 6-keto-prostaglandin F1alpha in all 4 groups, although the reduction was greater in the Ox+LS group than in the Ox+NS and Sh+LS groups, which in turn had a greater reduction than the Sh+NS group. RBF significantly decreased in every group except the Sh+NS group, but no effect on blood pressure, inulin clearance, or urinary sodium excretion was seen. The decrease in RBF was significantly greater in the Ox+LS group than in the Sh+LS and Ox+NS group. The decrease in RBF was dependent on cortical RBF in the Sh+LS and Ox+NS groups, and on both cortical and medullary RBF in the Ox+LS group. Estrogen replacement therapy reversed the ovariectomy-induced changes. Estrogen-dependent COX-2 expression plays an important role in the RBF regulation in female rats.

Differentiating between effects of streptozotocin per se and subsequent hyperglycemia on renal function and metabolism in the streptozotocin-diabetic rat model.

The animal model with streptozotocin (STZ)-induced diabetes mellitus is associated with progressive renal disturbances. The aim of this study was to differentiate between toxic effects of STZ and the effect of hyperglycemia. Previous studies have been limited to investigating the influence of STZ on glomerular filtration rate (GFR), albuminuria and renal morphology. The present study presents a new approach when transplanting beta-cells to cure the STZ-treated animals and extends the evaluation to include both renal function and oxygen metabolism. Animals were allocated to three groups: control animals, STZ-diabetic animals and animals rendered diabetic with an injection of STZ, followed by immediate syngeneic transplantation of approximately 1000 pancreatic islets into the splenic parenchyma. This latter procedure reversed the hyperglycemia induced by STZ. Renal function was evaluated from GFR and urinary albumin and protein leakage, while regional renal blood flow was determined using a laser-Doppler technique and oxygen tension measured with Clark-type electrodes. In diabetic animals, GFR increased, renal oxygen tension decreased and renal hypertrophy occurred, along with urinary leakage of protein, including albumin. Early transplantation of pancreatic islets to STZ-treated animals prevented the development of all these changes, except for proteinuria. However, an analysis of urinary protein content revealed that albuminuria was preventable by islet transplantation. We conclude that the urinary protein leakage in this animal model is at least partly due to direct toxic effects of STZ, whereas the other renal changes investigated in this study are due to the long-term diabetic condition.

Adenosine A1 receptors in contrast media-induced renal dysfunction in the normal rat.

Renal vasoconstriction with resultant tissue hypoxia, especially in the renal medulla, has been suggested to play a role in contrast media (CM)-induced nephropathy. In this study we investigated the effects of injection of the non-ionic low-osmolar CM iopromide with and without pretreatment with the selective adenosine A1-receptor antagonist DPCPX. The effects were evaluated on regional renal blood flow, outer medullary oxygen tension (PO2) and urine output in normal anaesthetised rats. A laser-Doppler technique was used for recording haemodynamic changes while oxygen microelectrodes were used for oxygen measurements. The A1-receptor antagonist per se elevated glomerular filtration rate (+44%), cortical blood flow (+15%) and urine output (threefold) while reducing outer medullary PO2 (-24%). Administration of CM reduced outer medullary blood flow (OMBF; -26%) and PO2 (-80%) but did not affect cortical blood flow. Urine output increased 28-fold by CM while arterial blood pressure was reduced. The CM-mediated effect on haemodynamics, PO2, urine output and blood pressure was unaffected by the A1-receptor antagonist. Adenosine A1-receptors are not important mediators of the depression of outer medullary blood flow and PO2 caused by the CM iopromide in the normal rat; however, A1-receptors are tonically active to regulate renal haemodynamics, PO2 and urine production during normal physiological conditions.

Comparison of pulsatile and non‐pulsatile cardiopulmonary bypass on regional renal blood flow in sheep

Objective—The purpose of the present study was to evaluate the effects of pulsatile cardiopulmonary bypass (CPB) on sheep regional renal blood flow by comparing pulsatile and non‐pulsatile perfusion at two different flow rates.Design—Seven female Suffolk sheep were used and the animals were perfused with pulsatile and non‐pulsatile CPB at flow rates of 60 and 100 ml/min/kg. Regional renal blood flow was measured by the colored microsphere method. General linear model ANOVA was performed to analyze the data.Results—Regional renal blood flow was significantly higher in both outer and middle cortices of pulsatile CPB compared with non‐pulsatile CPB (outer cortex: pulsatile CPB, 381 ± 192 ml/min/100 g, non‐pulsatile CPB, 255 ± 151 ml/min/100 g, p = 0.002; middle cortex: pulsatile CPB, 239 ± 114 ml/min/100 g, non‐pulsatile CPB, 176 ± 80 ml/min/100 g, p = 0.02). The increase of flow rate from 60 to 100 ml/min/kg improved renal cortical blood flow significantly.Conclusion—The regional renal blood flow was significantly higher in both outer and middle cortices of pulsatile CPB compared with the non‐pulsatile CPB.

Cyclooxygenase-2: A Potential Target in Human Cancer

Cyclooxygenase-2: A Potential Target in Human Cancer

Effect of High Glucose on Nitric Oxide Production and Endothelial Nitric Oxide Synthase Protein Expression in Human Glomerular Endothelial Cells

Background: Hyperglycemia directly contributes to the development of diabetic nephropathy. Nitric oxide (NO), a potent endothelium-derived vasodilator, has been suggested to participate in the regulation of renal blood flow, glomerular filtration rate, and mesangial matrix accumulation. Human vascular endothelial cells are known to exhibit functional heterogeneity, this prompted us to do the first study of NO bioavailability in human glomerular endothelial cells (HGECs), in response to high glucose exposure. Methods: NO release was examined by detecting nitrite generation by the Griess assay in HGECs exposed to control-level (5.5 mM) and high-level (15, 30 and 60 mM) glucose solutions at various time periods (24, 48 and 72 h) in the presence or absence of L-arginine (1 mM), or superoxide dismutase (SOD) (250 U/ml). In addition, we evaluated the effect of glucose on the expression of endothelial nitric oxide synthase (eNOS) in HGECs by Western blotting. Results: Final levels of nitrite generated in HGECs were reduced significantly, in a time- and concentration-dependent manner, after high glucose exposure. However, Western blot analysis revealed that eNOS protein expression was significantly upregulated at 12 h after exposure to high glucose concentrations (30 mM), reaching a peak at 48 h (twofold increase over baseline levels). The inhibitory effect of high glucose on NO production was restored by the addition of SOD. Addition of L-arginine (1 mM) to external media also reversed the inhibitory effect of high glucose on NO production of HGECs as well. Conclusions: The present study demonstrated that high glucose increased eNOS protein expression, but decreased NO release finally. Decreased NO bioavailability seems to be associated with overproduction of superoxide and L-arginine deficiency. These findings provide an important clue in clarifying the molecular basis of the mechanisms by which elevated glucose leads to an imbalance between NO and superoxide, resulting in impaired endothelial function. In addition, restoration of NO function by both administration of L-arginine and adequate intake of antioxidants suggests a potential supportive treatment for patients with diabetic nephropathy.

Lung cancer and cyclooxygenase-2

Lung cancer is by far the leading cause of cancer-related death. Overall survival is poor and has not improved substantially over the last half century. It is clear that new approaches are needed and these should include prevention, screening for early detection, and novel treatments based on our understanding of the molecular biology of this disease. Recently attention has been drawn to the role of the cyclooxygenase (COX) enzyme and its involvement in tumorigenesis. Investigations have documented two isoforms, COX-1 and COX-2, encoded by different genes. COX-1 is constitutively expressed in most tissues and appears to be responsible for the production of prostaglandins mediating normal physiologic functions, such as the maintenance of gastric mucosa and regulation of renal blood flow. In contrast, COX-2 is normally undetectable in most tissues, and is induced by cytokines, growth factors, oncogenes, and tumor promoters. A growing body of evidence indicates COX-2 plays a key role in lung cancer, and can serve as a potential marker of prognosis in this disease. Furthermore, the recent availability of COX-2 inhibitor medications offers a unique opportunity to interfere with the development of lung cancer and the progression of metastasis. Because COX-2 inhibitors have been demonstrated to interfere with tumorigenesis, the COX-2 enzyme may be an attractive target for therapeutic and chemoprotective strategies in lung cancer patients.

Newly developed techniques to study and diagnose acute renal failure.

Progress in treating human acute renal failure (ARF) is dependent on developing techniques that allow for the rapid diagnosis, quantification of injury, further understanding of the pathophysiology, and the effects of therapy. Therefore, four techniques that will facilitate this progress are described and illustrated by four different investigative teams. Techniques to measure rapid changes in GFR are available for rapid diagnosis and quantification of ARF in humans. State-of-the-art magnetic resonance imaging (MRI) presently allows for enhanced resolution of regional renal blood flow and functional evaluations in patients. Furthermore, new probes and techniques for MRI that allow for identification and quantitation of inflammation, applicable to human ARF, are being developed and tested in animal models. Finally, two-photon microscopy will allow for four-dimensional cellular and subcellular studies in animal models of ARF providing rapid insights into pathophysiology and the therapeutic effects of a variety of promising agents. Further development and utilization of these techniques, especially in concert with genetic, proteomic, and molecular approaches, will allow for needed insights into the pathophysiology and therapy in human ARF.

Reactive oxygen species cause diabetes-induced decrease in renal oxygen tension.

Augmented formation of reactive oxygen species (ROS) induced by hyperglycaemia has been suggested to contribute to the development of diabetic nephropathy. This study was designed to evaluate the influence of streptozotocin (STZ)-induced diabetes mellitus, as well as the effects of preventing excessive ROS formation by alpha-tocopherol treatment, on regional renal blood flow, oxygen tension and oxygen consumption in anaesthetized Wistar Furth rats. Non-diabetic and STZ-diabetic rats were investigated after 4 weeks with or without dietary treatment with the radical scavenger DL-alpha-tocopherol (vitamin E, 5%). A laser-Doppler technique was used to measure regional renal blood flow, whilst oxygen tension and consumption were measured using Clark-type microelectrodes. Renal oxygen tension, but not renal blood flow, was lower throughout the renal parenchyma of diabetic rats when compared to non-diabetic control rats. The decrease in oxygen tension was most pronounced in the renal medulla. Renal cellular oxygen consumption was markedly increased in diabetic rats, predominantly in the medullary region. Diabetes increased lipid peroxidation and protein carbonylation in the renal medulla. Treatment with alpha-tocopherol throughout the course of diabetes prevented diabetes-induced disturbances in oxidative stress, oxygen tension and consumption. The diabetic animals had a renal hypertrophy and a glomerular hyperfiltration, which were unaffected by alpha-tocopherol treatment. We conclude that oxidative stress occurs in kidneys of diabetic rats predominantly in the medullary region and relates to augmented oxygen consumption and impaired oxygen tension in the tissue.

The Role of Endogenous Endothelin in the Regulation of Uteroplacental and Renal Blood Flow During Pregnancy in Conscious Rats

Advancing pregnancy is characterized by a ten-fold increase in uterine blood flow and a 50 per cent increase in renal blood flow. To evaluate the involvement of endogenous endothelin (ET) in these haemodynamic changes the effect of bosentan, an ETA/B receptor antagonist, on uteroplacental and renal blood flow was studied in awake pregnant Sprague–Dawley rats. Regional blood flows were measured using microsphere technique immediately prior to and 30 min after bosentan administration (20 mg/kg i.v.). Four groups of animals (term: 23 days) were included: bosentan was administered to ten rats at gestation day (GD) 19 and nine at GD 20–21. In addition, four rats at GD 19 and five animals at GD 20–21 received saline and served as control groups. Basal placental blood flow increased significantly from 19 days' gestation to 20–21 days. Basal myometrial blood flow did not change with gestational age. At gestation day 19 bosentan increased placental and myometrial blood flow significantly (80 per cent and 43 per cent, respectively, P<0.05). This effect was not observed at gestation days 20–21. Renal blood flow did not change in response to bosentan at GD 19 but decreased by 20 per cent at GD 20–21 ( P<0.01). In conclusion, in the awake pregnant rat there is a significant endogenous ET dependent vasoconstrictor tone in the uteroplacental vessels that diminishes towards term. We speculate that this change in responsiveness to endogenous ET contribute to the increase in placental blood flow in late gestation.

Renal blood flow measurement with contrast-enhanced harmonic ultrasonography: evaluation of dopamine-induced changes in renal cortical perfusion in humans.

An accessible non-invasive method for evaluating renal regional blood flow in real time is highly desirable in the clinical setting. Recent progress in ultrasonography with microbubble contrast has allowed quantification of regional blood flow in animal models. Goal ofthis study was to establish a convenient contrast--enhanced harmonic ultrasonography (CEHU) method for evaluating renal cortical blood flow in humans. We carried out intermittent second harmonic imaging in 9 healthy volunteers. Pulse interval was progressively decreased from 4 s - 0.2 s during continuous venous infusion of the microbubble contrast agent. Pulse interval versus CEHU-derived acoustic intensity plots provided microbubble velocity (MV) and fractional vascular volume (FVV) during renal cortical perfusion in humans. Low-dose dopamine infusion (2 microg/min/kg) resulted in a significant increase in MV which correlated well with the increase in total renal blood flow (RBF) determined by a conventional study of p-aminohippurate clearance (C(PAH)) (r = 0.956, p < 0.0001). Although FVV was not significantly increased, alterations in CEHU-derived renal cortical blood flow calculated by the products of MV and FVV were also correlated with alterations in total RBF (r = 0.969, p < 0.0001). Thus, low-dose dopamine infusion increases renal cortical blood flow observed in CEHU, mainly by increasing MV. The present study shows that renal cortical blood flow in humans can be measured non-invasively by CEHU and that CEHU can be used for quantitatively evaluating changes induced by a therapeutic agent such as dopamine in flow velocity and in FVV.

Mechanisms of pressure natriuresis: how blood pressure regulates renal sodium transport.

An acute increase in blood pressure provokes a rapid decrease in proximal tubule salt and water reabsorption that is central to tubuloglomerular feedback regulation of renal blood flow and glomerular filtration rate and contributes to pressure natriuresis. The molecular mechanisms responsible for this critical homeostatic adjustment were studied. When blood pressure is acutely elevated, apical proximal tubule NHE3 are rapidly redistributed out of the microvilli to intermicrovillar clefts and then endosomal pools, and Na,K-ATPase activity is suppressed. Depressing apical Na(+) entry without hypertension is not sufficient to decrease Na,K-ATPase activity, and depressing Na,K-ATPase activity alone is not sufficient to decrease proximal tubule Na(+) and water reabsorption; thus, it appears that coordinated decreases in both NHE3 surface distribution and Na,K-ATPase activity may be important for the response to acute hypertension. Clamping plasma angiotensin II levels blunts the retraction of NHE3 from the cell surface to endosomal pools. The increased volume flow of salt and water to the loop of Henle stimulates Na,K-ATPase activity in this region and provides evidence for a downstream shift in sodium transport during acute hypertension. These same responses in the proximal tubule and loop develop and persist in the spontaneously hypertensive rat. These studies demonstrate that sodium transporters along the nephron are very dynamic, responding quickly to normal fluctuations of blood pressure, and are key to generating the macula densa tubuloglomerular feedback signal and for accommodating increased volume flow through the loop of Henle.

Quantification of renal perfusion abnormalities using an intravascular contrast agent (part 2): results in animals and humans with renal artery stenosis.

The interrelation between the morphologic degree of renal artery stenosis and changes in parenchymal perfusion is assessed using an intravascular contrast agent. In seven adult foxhounds, different degrees of renal artery stenosis were created with an inflatable clamp implanted around the renal artery. Dynamic susceptibility-weighted gradient-echo imaging was used to measure signal-time curves in the renal artery and the renal parenchyma during administration of 1.5 mg/kg BW of an intravascular ultrasmall particle iron oxide (USPIO) contrast agent. From the dynamic series, regional renal blood volume (rRBV), regional renal blood flow (rRBF), and mean transit time (MTT) were calculated. The morphologic degree of stenosis was measured in the steady state using a high-resolution 3D contrast-enhanced (CE) MR angiography (MRA) sequence (voxel size = 0.7 x 0.7 x 1 mm(3)). Five patients with renoparenchymal damage due to long-standing renal artery stenosis were evaluated. In the animal stenosis model, cortical perfusion remained unchanged for degrees of renal artery stenosis up to 80%. With degrees of stenoses > 80%, cortical perfusion dropped to 151 +/- 54 ml/100 g of tissue per minute as compared to a baseline of 513 +/- 76 ml/100 g/min. In the patients, a substantial difference in the cortical perfusion of more than 200 +/- 40 ml/100 g/min between the normal and the ischemic kidneys was found. The results show that quantitative renal perfusion measurements in combination with 3D-CE-MRA allow the functional significance of a renal artery stenosis to be determined in a single MR exam. Differentiation between renovascular and renoparenchymal disease thus becomes feasible.

Quantification of renal perfusion using an intravascular contrast agent (part 1): results in a canine model.

In this work absolute values of regional renal blood volume (rRBV) and flow (rRBF) are assessed by means of contrast-enhanced (CE) MRI using an intravascular superparamagnetic contrast agent. In an animal study, eight foxhounds underwent dynamic susceptibility-weighted MRI upon injection of contrast agent. Using principles of indicator dilution theory and deconvolution analysis, parametric images of rRBV, rRBF, and mean transit time (MTT) were computed. For comparison, whole-organ blood flow was determined invasively by means of an implanted flow probe, and the weight of the kidneys was evaluated postmortem. A mean rBV value of 28 ml/100 g was found in the renal cortex, with a corresponding mean rBF value of 524 ml/100 g/min and an average MTT of about 3.4 s. Although there was a systematic difference between the absolute blood flow values determined by MRI and the ultrasonic probe, a significant correlation (r(s) = 0.72, P < 0.05) was established. The influence of the arterial input function (AIF), T(1) relaxation effects, and repeated measurements on the precision of the perfusion quantitation is discussed.

Effects of the contrast medium iopromide on renal hemodynamics and oxygen tension in the diabetic rat kidney.

We investigated the effects of the contrast medium (CM) iopromide on regional renal blood flow and oxygen tension (pO2) in the streptozotocin (STZ)-induced diabetic Wistar Furth rats. In normoglycemic rats, CM injection induced a transient decrease followed by an increase in renal cortical blood flow (CBF), whereas CBF increased directly in the diabetic animals. Renal outer medullary blood flow (OMBF) increased in controls, while it decreased in the diabetic animals following CM injection. In control rats a marked initial decrease in OM pO2 following injection of CM was observed. In animals diabetic for 4 weeks only a slight decrease was seen, whereas in 9-week diabetic animals a persistent increase was recorded. An altered oxygen tension and hemodynamic response to CM was found in diabetic rats. If these disturbances may contribute to the development of renal dysfunction by CM in the diabetic rat kidney remains to be elucidated.

Advances in the pathophysiology of constitutive and inducible cyclooxygenases: two enzymes in the spotlight

The aim of this commentary is to discuss recent data on the role of prostaglandins generated by both constitutive and inducible cyclooxygenases (COXs). According to a popular hypothesis, COX-1 generates ‘good’ prostaglandins for physiological ‘housekeeping’ functions like gastrointestinal (GI) mucosal integrity and regulation of renal blood flow, while COX-2 forms the ‘bad’ prostaglandins responsible for inflammatory symptoms. However, recent data show that the biological functions of prostanoids formed by the two enzymes are much more complex and interrelated than previously appreciated. Experimental evidence indicates that a full inflammatory response is likely sustained by prostanoids generated by both enzymes, and an effective anti-inflammatory effect requires the inhibition of the two enzymes. Similarly, the selective inhibition of either COX-1 or COX-2 does not elicit GI damage, but inhibition of both enzymes is necessary for GI mucosal damage to develop. Prostaglandins generated by both enzymes contribute to normal renal function by regulating the vascular tone and the normal blood flow. The synthesis of endothelial prostacyclin is mainly driven by COX-2, so that the selective COX-2 inhibition may bias vascular prostaglandin synthesis in favour of COX-1-derived thromboxane A 2 in platelets, leading to a prothrombotic outcome. Moreover, prostaglandins formed by COX-2 appear to have a major role in myocardial protection. We propose that the complexity of the situation in the field of COX-derived mediators should be borne in mind when anti-inflammatory therapy is required.

ANTIOXIDANTS MODULATE ADENOSINE METABOLISM IN RAT MESANGIAL CELLS CULTURED UNDER HIGH GLUCOSE CONDITIONS

Glomerular mesangial cells play a major role in glomerular hemodynamics, considered also as antigen-presenting cells participating in immune response. Mesangial dysfunction and proliferation are typical lesions of diabetic glomerulopathy. Adenosine, a local hormone, produced by mesangial cells is a metabolic regulator of renal blood flow, capable of decreasing glomerular filtration rate (GFR), exerting immunosuppressive, antiproliferative and anti-inflammatory properties. Since it was well established that antioxidants confer protection against increased oxidative stress that occurs in diabetes, the effect of captopril, reduced glutathione and melatonin on adenosine metabolism was investigated. Glomerular mesangial cells obtained from collagenase treated glomeruli, isolated from renal cortex of Sprague-Dowley rats, were grown under high glucose conditions (30 mmol/L) as a model of diabetic microenvironment. The activity of adenosine metabolizing enzymes: 5′-nucleotidease (5′-NU) responsible for its production and adenosine deaminase (ADA)—responsible for its degradation were investigated. Hyperglycemic conditions led to decreased adenosine production via 5′-NU and decreased removal via ADA. Captopril, given in therapeutic concentration induced enzyme activities in normoglycemic conditions and restored hyperglycemia—induced decrease. In order to investigate if the presence of SH groups may be responsible for this improvement, the cells were exposed to reduced glutathione, and it exerted almost equal effect, given in physiological and higher concentrations. Melatonin increased 5′-NU activity only in physiological glucose conditions. Presented results confirm potential renoprotective effect of SH-group containing antioxidant supplementation during diabetes in restoring adenosine metabolism.

Effects of Dopamine Infusion on Cardiac and Renal Blood Flows in Dogs

In veterinary medicine, dopamine is currently being administered clinically by infusion for treatment of kidney disorders at low doses (< or = 3 microg/kg/min) and for assessment of hemodynamics at high doses (> or = 5 microg/kg/min). However, since high doses of dopamine cause peripheral vasoconstriction due to its effect on alpha adrenoceptors, high doses have no longer been recommended. The present study was conducted to explore possible regimens for the use of dopamine infusion in dogs. The regional (renal and cardiac) blood flow for 60 min was measured by using colored microspheres at three doses (3, 10 and 20 microg/kg/min) of dopamine infusion in healthy anesthetized mongrel dogs. The effects on kidney and peripheral hemodynamics at each dose and the resultant cardiac output, mean arterial blood pressure and total peripheral resistance were determined. Renal blood flow increased markedly at 3 microg/kg/min dopamine. Improvement in hemodynamics indicated by marked increase in cardiac blood flow, cardiac output and mean arterial blood pressure and decreased total peripheral resistance was observed at higher doses (10 and 20 microg/kg/min). At 10 microg/kg/min, in addition to the satisfactory increase in cardiac blood flow, there was also a stable satisfactory increase in renal blood flow. However, at 20 microg/kg/min, increased myocardial oxygen consumption (manifested by marked increased in cardiac output), arrythmia and irregular increase in renal blood flow were detected. This study suggests that the clinical use of dopamine infusion in dogs could be safely expanded to moderately higher doses.

537 The role of endogenous endothelin in the regulation of uteroplacental and renal blood flow during late pregnancy in the rat

537 The role of endogenous endothelin in the regulation of uteroplacental and renal blood flow during late pregnancy in the rat

An autoradiographic study of regional blood flow distribution in the rat kidney during ureteric obstruction--the role of vasoactive compounds.

To determine the changes in regional renal blood flow during ureteric obstruction and to examine the role of vasoactive mediators in effecting these changes. Renal blood flow in Sprague-Dawley rats was assessed after periods of ureteric obstruction using a quantitative autoradiographic technique based on Kety's theory of diffusion of an inert tracer (14C-iodoantipyrine). Prostaglandins, thromboxanes and renin-angiotensin were inhibited pharmacologically using diclofenac sodium and enalapril. Baseline blood flow to the outer cortex, inner cortex and medulla was 807, 258 and 105 mL/100 g/min, respectively. There was an increase in outer cortical blood flow after 10 min of ureteric obstruction which became significant at 30 min (P < 0.05). There was a significant decrease in inner cortical and medullary blood flow at 30 min, to 210 and 68 mL/100 g/min, respectively (P < 0.05). Diclofenac sodium abolished the increase in outer cortical blood flow. After 24 h of unilateral ureteric obstruction, outer cortical blood flow decreased to 492 mL/100 g/min; inner cortical blood flow also decreased but to a lesser extent, to 190 mL/100 g/min. Inhibition of prostaglandins, thromboxanes and the renin-angiotensin system reduced the degree of renal vasoconstriction but there was still a significant decrease in outer cortical perfusion despite the presence of these blocking agents. The control of the renal vasculature involves a complex interplay between a variety of vasoactive mediators. Quantitative autoradiography offers the opportunity to evaluate changes in regional renal perfusion with high resolution and will allow a greater understanding of the pathophysiology of renal diseases.