Contrast gain control is a reparameterization of a population response curve.

Neurons in primary visual cortex (area V1) adapt in varying degrees to the average contrast of the environment, suggesting that the representation of visual stimuli may interact with the state of cortical gain control in complex ways. To investigate this possibility, we measured and analyzed the responses of neural populations in mouse V1 to visual stimuli as a function of contrast in different environments, each characterized by a unique distribution of contrast values. Our findings reveal that, for a fixed stimulus, the population response can be described by a vector function r(gec), where the gain ge is a decreasing function of the mean contrast of the environment. Thus, gain control can be viewed as a reparameterization of a population response curve, which is invariant across environments. Different stimuli are mapped to distinct curves, all originating from a common origin, corresponding to a zero-contrast response. Altogether, our findings provide a straightforward, geometric interpretation of contrast gain control at the population level and show that changes in gain are well-matched among members of a population.

Criticality in probabilistic models of spreading dynamics in brain networks: Epileptic seizures.

The spread of seizures across brain networks is the main impairing factor, often leading to loss-of-consciousness, in people with epilepsy. Despite advances in recording and modeling brain activity, uncovering the nature of seizure spreading dynamics remains an important challenge to understanding and treating pharmacologically resistant epilepsy. To address this challenge, we introduce a new probabilistic model that captures the spreading dynamics in patient-specific complex networks. Network connectivity and interaction time delays between brain areas were estimated from white-matter tractography. The model's computational tractability allows it to play an important complementary role to more detailed models of seizure dynamics. We illustrate model fitting and predictive performance in the context of patient-specific Epileptor networks. We derive the phase diagram of spread size (order parameter) as a function of brain excitability and global connectivity strength, for different patient-specific networks. Phase diagrams allow the prediction of whether a seizure will spread depending on excitability and connectivity strength. In addition, model simulations predict the temporal order of seizure spread across network nodes. Furthermore, we show that the order parameter can exhibit both discontinuous and continuous (critical) phase transitions as neural excitability and connectivity strength are varied. Existence of a critical point, where response functions and fluctuations in spread size show power-law divergence with respect to control parameters, is supported by mean-field approximations and finite-size scaling analyses. Notably, the critical point separates two distinct regimes of spreading dynamics characterized by unimodal and bimodal spread-size distributions. Our study sheds new light on the nature of phase transitions and fluctuations in seizure spreading dynamics. We expect it to play an important role in the development of closed-loop stimulation approaches for preventing seizure spread in pharmacologically resistant epilepsy. Our findings may also be of interest to related models of spreading dynamics in epidemiology, biology, finance, and statistical physics.

Contrast gain control is a reparameterization of a population response curve.

Neurons in primary visual cortex (area V1) adapt in different degrees to the average contrast of the environment, suggesting that the representation of visual stimuli may interact with the state of cortical gain control in complex ways. To investigate this possibility, we measured and analyzed the responses of neural populations to visual stimuli as a function of contrast in different environments, each characterized by a unique distribution of contrast. Our findings reveal that, for a given stimulus, the population response can be described by a vector function r ( g e c ) , where the gain g e is a decreasing function of the mean contrast of the environment. Thus, gain control can be viewed as a reparameterization of a population response curve, which is invariant across environments. Different stimuli are mapped to distinct curves, all originating from a common origin, corresponding to a zero-contrast response. Altogether, our findings provide a straightforward, geometric interpretation of contrast gain control at the population level and show that changes in gain are well coordinated among members of a neural population.

A rapid, controlled-environment seedling root screen for wheat correlates well with rooting depths at vegetative, but not reproductive, stages at two field sites.

BACKGROUND AND AIMS: Root length and depth determine capture of water and nutrients by plants, and are targets for crop improvement. Here we assess a controlled-environment wheat seedling screen to determine speed, repeatability and relatedness to performance of young and adult plants in the field. METHODS: Recombinant inbred lines (RILs) and diverse genotypes were grown in rolled, moist germination paper in growth cabinets, and primary root number and length were measured when leaf 1 or 2 were fully expanded. For comparison, plants were grown in the field and root systems were harvested at the two-leaf stage with either a shovel or a soil core. From about the four-leaf stage, roots were extracted with a steel coring tube only, placed directly over the plant and pushed to the required depth with a hydraulic ram attached to a tractor. KEY RESULTS: In growth cabinets, repeatability was greatest (r = 0.8, P < 0.01) when the paper was maintained moist and seed weight, pathogens and germination times were controlled. Scanned total root length (slow) was strongly correlated (r = 0.7, P < 0.01) with length of the two longest seminal axile roots measured with a ruler (fast), such that 100-200 genotypes were measured per day. Correlation to field-grown roots at two sites at two leaves was positive and significant within the RILs and cultivars (r = 0.6, P = 0.01), and at one of the two sites at the five-leaf stage within the RILs (r = 0.8, P = 0.05). Measurements made in the field with a shovel or extracted soil cores were fast (5 min per core) and had significant positive correlations to scanner measurements after root washing and cleaning (>2 h per core). Field measurements at two- and five-leaf stages did not correlate with root depth at flowering. CONCLUSIONS: The seedling screen was fast, repeatable and reliable for selecting lines with greater total root length in the young vegetative phase in the field. Lack of significant correlation with reproductive stage root system depth at the field sites used in this study reflected factors not captured in the screen such as time, soil properties, climate variation and plant phenology.

Pre- or post-treatment with aminoguanidine attenuates a renal distal acidification defect induced by acute ureteral obstruction in rats.

Acute unilateral ureteral obstruction (UUO) impairs distal nephron acid secretion and stimulates expression of inducible nitric oxide synthase (iNOS) in post-obstructed kidney (POK). This study investigated the influence of pre- or post-treatment with aminoguanidine as a selective iNOS inhibitor on UUO-induced renal functional disturbances. To induce acute UUO, the left ureter in rats was ligated and released after 24 h. Then, a 3 h clearance period followed by bicarbonate loading and thereafter a 30 min clearance period were allocated. Aminoguanidine was administered either prior to the UUO induction or after release of the obstruction in the different rat groups, while untreated and sham groups received normal saline. During the first clearance period, fractional bicarbonate excretion and urinary pH increased markedly in the POK of the untreated group compared with the left kidney of sham group, and a large drop in the difference between urine and blood pCO2 (U-B pCO2) was observed after bicarbonate loading; all of these parameters were ameliorated in the pre-treated and post-treated groups. However, the UUO-induced decreases in creatinine clearance, sodium reabsorption, urine osmolality, and free-water reabsorption in the POK were attenuated only in the post-treated group. Therefore, the in vivo application of a selective iNOS inhibitor partially improved the acute UUO-induced distal nephron acidification defect, while post-treatment but not pre-treatment with aminoguanidine ameliorated decrements of glomerular filtration, sodium reabsorption, and urine-concentrating ability.

Feedback phase correction of Bessel beams in confocal line light-sheet microscopy: a simulation study.

Confocal line detection has been shown to improve contrast in light-sheet-based microscopy especially when illuminating the sample by Bessel beams. Besides their self-reconstructing capability, the stability in propagation direction of Bessel beams allows to block the unwanted emission light from the Bessel beam's ring system. However, due to phase aberrations induced especially at the border of the specimen, Bessel beams may not propagate along lines parallel to the slit detector. Here we present a concept of how to correct the phase of each incident Bessel beam such that the efficiency of confocal line detection is improved by up to 200%-300%. The applicability of the method is verified by the results obtained from numerical simulations based on the beam propagation method.

Linear feedback control of spreading dynamics in stochastic nonlinear network models: epileptic seizures.

The development of models and approaches for controlling the spreading dynamics of epileptic seizures is an essential step towards new therapies for people with pharmacologically resistant epilepsy. Beyond resective neurosurgery, in which epileptogenic zones (EZs) are the target of surgery, closed-loop control based on intracranial electrical stimulation, applied at the very early stage of seizure evolution, has been the main alternative, e.g. the RNS system from NeuroPace (Mountain View, CA). In this approach the electrical stimulation is delivered to target brain areas after detection of seizure initiation in the EZ. Here, we examined, on model simulations, some of the closed-loop control aspects of the problem. Seizure dynamics and spread are typically modeled with highly nonlinear dynamics on complex brain networks. Despite the nonlinearity and complexity, currently available optimal feedback control approaches are mostly based on linear approximations. Alternative machine learning control approaches might require amounts of data beyond what is commonly available in the intended application. We thus examined how standard linear feedback control approaches perform when applied to nonlinear models of neural dynamics of seizure generation and spread. In particular, we considered patient-specific epileptor network models for seizure onset and spread. The models incorporate network connectivity derived from (diffusion MRI) white-matter tractography, have been shown to capture the qualitative dynamics of epileptic seizures and can be fit to patient data. For control, we considered simple linear quadratic Gaussian (LQG) regulators. The LQG control was based on a discrete-time state-space model derived from the linearization of the patient-specific epileptor network model around a stable fixed point in the regime of preictal dynamics. We show in simulations that LQG regulators acting on the EZ node during the initial seizure period tend to be unstable. The LQG solution for the control law in this case leads to global feedback to the EZ-node actuator. However, if the LQG solution is constrained to depend on only local feedback originating from the EZ node itself, the controller is stable. In this case, we demonstrate that localized LQG can easily terminate the seizure at the early stage and prevent spread. In the context of optimal feedback control based on linear approximations, our results point to the need for investigating in more detail feedback localization and additional relevant control targets beyond epileptogenic zones.

Effects of hypercapnia and NO synthase inhibition in sustained hypoxic pulmonary vasoconstriction.

BACKGROUND: Acute respiratory disorders may lead to sustained alveolar hypoxia with hypercapnia resulting in impaired pulmonary gas exchange. Hypoxic pulmonary vasoconstriction (HPV) optimizes gas exchange during local acute (0-30 min), as well as sustained (> 30 min) hypoxia by matching blood perfusion to alveolar ventilation. Hypercapnia with acidosis improves pulmonary gas exchange in repetitive conditions of acute hypoxia by potentiating HPV and preventing pulmonary endothelial dysfunction. This study investigated, if the beneficial effects of hypercapnia with acidosis are preserved during sustained hypoxia as it occurs, e.g in permissive hypercapnic ventilation in intensive care units. Furthermore, the effects of NO synthase inhibitors under such conditions were examined. METHOD: We employed isolated perfused and ventilated rabbit lungs to determine the influence of hypercapnia with or without acidosis (pH corrected with sodium bicarbonate), and inhibitors of endothelial as well as inducible NO synthase on acute or sustained HPV (180 min) and endothelial permeability. RESULTS: In hypercapnic acidosis, HPV was intensified in sustained hypoxia, in contrast to hypercapnia without acidosis when HPV was amplified during both phases. L-NG-Nitroarginine (L-NNA), a non-selective NO synthase inhibitor, enhanced acute as well as sustained HPV under all conditions, however, the amplification of sustained HPV induced by hypercapnia with or without acidosis compared to normocapnia disappeared. In contrast 1400 W, a selective inhibitor of inducible NO synthase (iNOS), decreased HPV in normocapnia and hypercapnia without acidosis at late time points of sustained HPV and selectively reversed the amplification of sustained HPV during hypercapnia without acidosis. Hypoxic hypercapnia without acidosis increased capillary filtration coefficient (Kfc). This increase disappeared after administration of 1400 W. CONCLUSION: Hypercapnia with and without acidosis increased HPV during conditions of sustained hypoxia. The increase of sustained HPV and endothelial permeability in hypoxic hypercapnia without acidosis was iNOS dependent.

Critical dynamics in the spread of focal epileptic seizures: Network connectivity, neural excitability and phase transitions.

Focal epileptic seizures can remain localized or, alternatively, spread across brain areas, often resulting in impairment of cognitive function and loss of consciousness. Understanding the factors that promote spread is important for developing better therapeutic approaches. Here, we show that: (1) seizure spread undergoes "critical" phase transitions in models (epileptor-networks) that capture the neural dynamics of spontaneous seizures while incorporating patient-specific brain network connectivity, axonal delays and identified epileptogenic zones (EZs). We define a collective variable for the spreading dynamics as the spread size, i.e. the number of areas or nodes in the network to which a seizure has spread. Global connectivity strength and excitability in the surrounding non-epileptic areas work as phase-transition control parameters for this collective variable. (2) Phase diagrams are predicted by stability analysis of the network dynamics. (3) In addition, the components of the Jacobian's leading eigenvector, which tend to reflect the connectivity strength and path lengths from the EZ to surrounding areas, predict the temporal order of network-node recruitment into seizure. (4) However, stochastic fluctuations in spread size in a near-criticality region make predictability more challenging. Overall, our findings support the view that within-patient seizure-spread variability can be characterized by phase-transition dynamics under transient variations in network connectivity strength and excitability across brain areas. Furthermore, they point to the potential use and limitations of model-based prediction of seizure spread in closed-loop interventions for seizure control.

L-carnitine improves oxidative stress and suppressed energy metabolism but not renal dysfunction following release of acute unilateral ureteral obstruction in rat.

BACKGROUND AND AIM: We recently showed that L-carnitine reduced oxidative stress and suppressed energy metabolism, while α-tocopherol only prevented redox imbalance, in the obstructed kidney of rats subjected to 24-hr of unilateral ureteral obstruction (UUO). The present study was undertaken to investigate the effects of both compounds on disturbed renal hemodynamics, solutes-excretion, and urine-concentrating ability as well as renal oxidative stress and suppressed metabolism at early hours following release of 24-hr UUO. METHODS: UUO was induced in anaesthetized rats that received L-carnitine, α-tocopherol or their vehicles in four different groups. Each rat was re-anaesthetized, prepared for renal functional measurements, and its ureteral obstruction was released at 24-hr. Then, urines of both kidneys were separately collected during 30-90 min of post-release, with taking blood samples at beginning and end of it. Finally, both kidneys were removed and preserved at -80°C for future measuring their levels of ATP and ADP as well as malondialdehyde (MDA) and ferric reducing/antioxidant power (FRAP). There were also sham and control groups. RESULTS: Post-obstructed kidney (POK) of vehicle-treated groups compared to equivalent kidney of sham group had lower ATP, ATP/ADP, FRAP, creatinine clearance, absolute Na(+)- and K(+)-excretion, and effective free-water reabsorption, but higher MDA and ADP. L-carnitine could improve oxidative stress and suppressed energy metabolism and α-tocopherol normalized redox state, but both compounds did not have any effects on altered functional variables of the POK. CONCLUSION: Oxidative stress and suppressed energy metabolism may not be involved in the development of renal dysfunction during acute ureteral obstruction.

Colonic stenting in 2011.

Self expanding metal stents (SEMS) are an established treatment in the management of malignant obstructing lesions throughout the gastrointestinal tract. SEMS have been utilized both as palliation in and as a bridge to surgical resection for malignant colonic obstruction. Many studies have demonstrated that placement of SEMS for malignant colonic obstruction is both efficacious, with high technical and clinical success rates, and safe with a low complication rate. In contrast, there is a paucity of data on the role of SEMS in the management of benign colonic obstruction, an indication which remains controversial. This review outlines the most recent developments in colonic stenting, their current indications, and the evidence to support their use in these indications.

A unifying framework for mean-field theories of asymmetric kinetic Ising systems.

Kinetic Ising models are powerful tools for studying the non-equilibrium dynamics of complex systems. As their behavior is not tractable for large networks, many mean-field methods have been proposed for their analysis, each based on unique assumptions about the system's temporal evolution. This disparity of approaches makes it challenging to systematically advance mean-field methods beyond previous contributions. Here, we propose a unifying framework for mean-field theories of asymmetric kinetic Ising systems from an information geometry perspective. The framework is built on Plefka expansions of a system around a simplified model obtained by an orthogonal projection to a sub-manifold of tractable probability distributions. This view not only unifies previous methods but also allows us to develop novel methods that, in contrast with traditional approaches, preserve the system's correlations. We show that these new methods can outperform previous ones in predicting and assessing network properties near maximally fluctuating regimes.

The roles played by IL-10, IL-23 and IL-17A in term delivery.

BACKGROUND: The immune system significantly participates in the development of the successful delivery process. The roles played by cytokine molecules in the induction of term delivery are yet to be clarified. The aim of this project was to explore the serum levels of interleukin-10 (IL-10), IL-17A, and IL-23 in the mothers with term and prolonged pregnancy and their infants. MATERIALS AND METHODS: In this study, 60 samples were collected from either mothers with term and prolonged pregnancy or their infants, collectively 240 samples. Serum levels of IL-10, IL-17A and IL-23 were explored using enzyme linked immunosorbent assay (ELISA) technique. RESULTS: IL-10 serum levels significantly decreased in the neonates with prolonged pregnancy when compared to their mothers. Serum levels of IL-23 were increased either in term or prolonged pregnancy neonates when compared to their corresponded mothers. Serum levels of IL-10 and IL-23 significantly decreased and increased, respectively, in the female in comparison to male in the prolonged pregnancy neonates. IL-10 also significantly decreased in the term mothers who had higher gravidity. CONCLUSION: Although, IL-17A does not play a key role in the delivery mechanism, IL-10 and IL-23 may be considered as potential factors in the modulation of term delivery.

Semimetal to semiconductor transition in Bi/TiO2 core/shell nanowires.

We demonstrate the full thermoelectric and structural characterization of individual bismuth-based (Bi-based) core/shell nanowires. The influence of strain on the temperature dependence of the electrical conductivity, the absolute Seebeck coefficient and the thermal conductivity of bismuth/titanium dioxide (Bi/TiO2) nanowires with different diameters is investigated and compared to bismuth (Bi) and bismuth/tellurium (Bi/Te) nanowires and bismuth bulk. Scattering at surfaces, crystal defects and interfaces between the core and the shell reduces the electrical conductivity to less than 5% and the thermal conductivity to less than 25% to 50% of the bulk value at room temperature. On behalf of a compressive strain, Bi/TiO2 core/shell nanowires show a decreasing electrical conductivity with decreasing temperature opposed to that of Bi and Bi/Te nanowires. We find that the compressive strain induced by the TiO2 shell can lead to a band opening of bismuth increasing the absolute Seebeck coefficient by 10% to 30% compared to bulk at room temperature. In the semiconducting state, the activation energy is determined to |41.3 ± 0.2| meV. We show that if the strain exceeds the elastic limit the semimetallic state is recovered due to the lattice relaxation.

Quantification of dyspnoea using descriptors: development and initial testing of the Dyspnoea-12.

RATIONALE: Dyspnoea is a debilitating and distressing symptom that is reflected in different verbal descriptors. Evidence suggests that dyspnoea, like pain perception, consists of sensory quality and affective components. The objective of this study was to develop an instrument that measures overall dyspnoea severity using descriptors that reflect its different aspects. METHODS: 81 dyspnoea descriptors were administered to 123 patients with chronic obstructive pulmonary disease (COPD), 129 with interstitial lung disease and 106 with chronic heart failure. These were reduced to 34 items using hierarchical methods. Rasch analysis informed decisions regarding further item removal and fit to the unidimensional model. Principal component analysis (PCA) explored the underlying structure of the final item set. Validity and reliability of the new instrument were further assessed in a separate group of 53 patients with COPD. RESULTS: After removal of items with hierarchical methods (n = 47) and items that failed to fit the Rasch model (n = 22), 12 were retained. The "Dyspnoea-12" had good internal reliability (Cronbach's alpha = 0.9) and fit to the Rasch model (chi(2) p = 0.08). Items patterned into two groups called "physical"(n = 7) and "affective"(n = 5). In the separate validation study, Dyspnoea-12 correlated with the Hospital Anxiety and Depression Scale (anxiety r = 0.51; depression r = 0.44, p<0.001, respectively), 6-minute walk distance (r = -0.38, p<0.01) and MRC (Medical Research Council) grade (r = 0.48, p<0.01), and had good stability over time (intraclass correlation coefficient = 0.9, p<0.001). CONCLUSION: Dyspnoea-12 fulfills modern psychometric requirements for measurement. It provides a global score of breathlessness severity that incorporates both "physical" and "affective" aspects, and can measure dyspnoea in a variety of diseases.

Comparison of the effects of L: -carnitine and alpha-tocopherol on acute ureteral obstruction-induced renal oxidative imbalance and altered energy metabolism in rats.

The suppression of renal energy metabolism during ureteral obstruction is a well-known phenomenon; however, its exact responsible mechanism(s) and association with simultaneously induced renal oxidative stress have not been clarified. This study examined the improving effects of L: -carnitine, a facilitating cofactor for mitochondrial oxidation of fatty-acids as well as a scavenger of free-radicals, and alpha-tocopherol as the most potent antioxidant on renal metabolic defect and oxidative stress induced by acute unilateral ureteral obstruction (UUO). The left ureter was ligated in ether-anaesthetised rats, in which L: -carnitine, alpha-tocopherol or their vehicles were intraperitoneally injected in four different groups. After elapsing 24 h of UUO-induction, both kidneys were removed and stored at -80 degrees C. There were also two sham-operated and control groups. The kidney samples were assessed to measure the levels of ferric reducing/antioxidant power (FRAP) and malondialdehyde (MDA) for evaluating their redox state, as well as, their amounts of adenosine triphosphate (ATP) and adenosine diphosphate (ADP) by using luciferin-luciferase method. As much as 24 h of UUO in vehicle-treated groups caused increases in MDA and ADP, but decreases in FRAP, ATP, and ATP/ADP of the obstructed kidney with respect to those of the sham group. alpha-tocopherol normalised the levels of MDA and FRAP but did not affect the altered amounts of energy metabolic indices in the obstructed kidney, while L: -carnitine could ameliorate all of them. These findings suggest that oxidative stress may not involve in development of acute UUO-induced suppression of renal aerobic metabolism, and probably reduction of energy substrates is a responsible factor.

Cooperative mechanisms of acute antidiuretic response to bendroflumethiazide in rats with lithium-induced nephrogenic diabetes insipidus.

The exact mechanism underlying thiazides-induced paradoxical antidiuresis in diabetes insipidus is still elusive, but it has been hypothesized that it is exerted either via Na+-depletion activating volume-homeostatic reflexes to decrease distal delivery, or direct stimulation of distal water reabsorption. This study examined how these two proposed mechanisms actually cooperate to induce an acute bendroflumethiazide (BFTZ)-antidiuretic effect in nephrogenic diabetes insipidus (NDI). Anaesthetized rats with lithium (Li)-induced NDI were prepared in order to measure their renal functional parameters, and in some of them, bilateral renal denervation (DNX) was induced. After a 30 min control clearance period, we infused either BFTZ into 2 groups, NDI+BFTZ and NDI/DNX+BFTZ, or its vehicle into a NDI+V group, and six 30 min experimental clearance periods were taken. During BFTZ infusion in the NDI+BFTZ group, transiently elevated Na+ excretion was associated with rapidly increased urinary osmolality and decreased free water clearance, but Li clearance and urine flow declined in the later periods. However, in the NDI/DNX+BFTZ group, there was persistently elevated Na+ excretion with unchanged Li clearance and urine flow during the experimental period, while alterations in free water clearance and urinary osmolality resembled those in the NDI+BFTZ group. In conclusion, BFTZ initially exerted two direct effects of natriuresis-diuresis and stimulating free water reabsorption at the distal nephron in NDI, which together elevated Na+ excretion and urinary osmolality but kept the urine volume unchanged in the first hour. Thereafter, the resultant sodium depletion led to the activation of neural reflexes that reduced distal fluid delivery to compensate for BFTZ-induced natriuresis-diuresis which, in cooperation with the direct distal BFTZ-antidiuretic effect, resulted in excretion of urine with a low volume, high osmolality, and normal sodium.

Researching breathlessness in palliative care: consensus statement of the National Cancer Research Institute Palliative Care Breathlessness Subgroup.

Breathlessness is common in advanced disease and can have a devastating impact on patients and carers. Research on the management of breathlessness is challenging. There are relatively few studies, and many studies are limited by inadequate power or design. This paper represents a consensus statement of the National Cancer Research Institute Palliative Care Breathlessness Subgroup. The aims of this paper are to facilitate the design of adequately powered multi-centre interventional studies in breathlessness, to suggest a standardised, rational approach to breathlessness research and to aid future 'between study' comparisons. Discussion of the physiology of breathlessness is included.

Early renal post-ischaemic tissue damage and dysfunction with contribution of A1-adenosine receptor activation in rat.

AIM: This study investigated the effect of a selective A(1)-adenosine receptor (A(1)-AR) antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), on the renal dysfunction and histological damage induced by ischaemia/reperfusion at an early stage. METHODS: Pentobarbital anaesthetised rats were prepared for measuring renal functional variables. Ischaemia was induced by bilateral renal artery clamping for 30 min followed by a 4 h reperfusion period. In DPCPX-treated rats, it was infused (i.v.) at 10 microg/kg per min before and after renal ischaemia. Both kidneys were examined using light and electron microscopy. RESULTS: The renal ischaemic challenge resulted in major histological and ultrastructural damages, which were associated with decreased creatinine clearance, absolute potassium-excretion and effective free-water reabsorption, but increased fractional sodium-excretion and urine flow during reperfusion period. In DPCPX-treated rats, the histological and ultrastructural damage to the kidneys was improved along with the decrease in creatinine clearance and increase in fractional sodium-excretion being smaller, but the increase in urine flow being larger than those of the non-treated rats, while absolute potassium-excretion and effective free-water reabsorption were equal to those of the sham-operated rats. CONCLUSION: These findings suggest that endogenous activation of A(1)-AR contributes to the early development of renal ischaemia/reperfusion injury.