Conference Publication Details
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Margham, Y and Johns, E;
Physiological Society General Meeting
Impact of reactive oxygen species on renal function in anaesthetised rats.
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Reactive oxygen species (ROS) are a product of mutochondral respiration undertaken by a number of enzymes such as xanthine oxidase and NADPH oxidase. Although the level of one ROS, superoxide anions, is limited by the enzyme superoxide dismutase (SOD), it can affect physiological processes.There is in vitro evidence (Gavin et al) that superoxide ions act directly to suppress epithelial transport along the nephron. The aim of this study was to examine in vivo the impact of either increasing the level of SOD, or following inhibition of its action on renal haemodynamic and excretory function. Male Wistar rats (250-320g) were anaesthetised with 1ml i.p. chloralose/urethane (16.5/250 mg/ml) and cannulae were inserted into the right femoral artery, to measure mean arterial pressure (MAP), and vein to infuse saline (9g/lNaCl) at 3ml/h. The left kidney was exposed via the flank, its ureter cannulated and an ultrasonic flowprobe fitted to the renal artery. A small cannula was inserted into the cortex for 4.5 ml to lie at the cortico-medullary boarder for the infusion of drugs (1.0 ml/h intra-renally, i.r.). At the end of surgery, the i.v. saline was replaced with saline plus inulin (2g/l) for measurement of glomerular filtration rate (GFR) and the animals were allowed 1-2 h to recover. A 30 min basal urine collection was taken and thereafter an i.v. infusion of either tempol (a SOD mimetic) at 30 μmmol/kg/min, or diethyl - dithio-carbamate (DETC) at 2mg/kg/min was begun. After 30 min, a further 30 min urine collection was taken, the i.r. infusion was stopped and a 30 min recovery clearance was taken. Data, mean±S.E.M. were taken as significant when P<0.05 (ANOVA). Infusion of tempol i.r. (n=5) had no effect on MAP, at 949± mmHg and was unchanged in the recovery period. Under these conditions there was a rise (P<0.05) in GFR, from 7.6±2.8 ml/min/kg, of 100% which was accompanied by increase in both urine flow, from 37.61±1.2 to 79.4±24.5 ml/min/kg, and absolute sodium excretion, from 2.6±0.9 to 8.22±.3 μmol/kg/min (both P<0.05). Administration of DETC (n=6) was without effect on MAP but caused decreases in GFR, of some 40%, urine flow of some 30% and sodium excretion of 50% (all P<0.05). These findings show that scavenging of superoxide anions within the kidney results in a marked increase in glomerular filtration and excretion of fluid and conversely blockade of SOD reduces filtration and fluid excretion. The changes in glomerular filtered load is most likely responsible for the changes in fluid excretion but this remains to be resolved.
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