Conference Publication Details
Mandatory Fields
Ahameda, A, O'Reilly, E and JohnsEJ;
Physiological Society General Meeting
Regulation of renal haemodynamics by reactive oxygen species in anaesthetised rats: a direct or indirect action via nitric oxide?
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The regulation of the blood flow through the cortex and medulla of the kidney is dependent on a range of factors one of which may be the level of oxidative stress that can modulate vascular tone. Previously (Ahmeda and Johns, 2004), we demonstrated that blockade of superoxide dismutase (SOD) within the kidney decreased perfusion of blood through both the cortex and medulla. This study aimed to investigate whether the vasoconstriction developed when superoxide anion production was increased was a consequence of a direct action on the blood vessels or an indirect one due to scavenging of nitric oxide (NO). Groups (n=6) of male Wistar rats (250-300 g) fed a normal (0.3% Na+) or high salt (3% Na+) diet, were anaesthetised with 1 ml i.p. chloralose/urethane (16.5/250 mg/ml, respectively) and supplemented as required. The right femoral vein and artery were cannulated for infusion of saline (154 mM NaCl) at 3 ml/h, and measurement of arterial blood pressure (BP). The left kidney was exposed via a flank incision, placed in a holder and a small cannula inserted 4.5 mm into the kidney for intramedullary (i.m.) infusion of drugs at 0.6-1.0 ml/h. Two Laser-Doppler microprobes were inserted 1.5 and 4.0 mm into the kidney to measure cortical (CP) and medullary (MP) blood perfusion, respectively After 90min, baseline values were taken then either diethyl-dithio-carbamate (DETC), a SOD inhibitor, 1, 2, and 4 mg/kg/min or a combination of DETC plus L-NAME (Nitric oxide synthase, NOS, inhibitor) 10 μg/kg/min were infused i.m. for 30 min. At the end of the experiments the animals were killed with an anaesthetic overdose. Data SEM were subjected to the Student′s t-test and significance taken at P<0.05. Baseline BP was similar in both normal and high salt rats, 1105 and 1206 mmHg, as was CP, 23030 PU versus 20828 PU but MP was lower in the high salt compared to the normal salt rats, 475 PU versus 626 PU (P<0.05). Infusion of DETC in the normal salt rats decreased CP and MP by 238% and 237% (both P<0.05), whereas in the high salt group CP fell by 154% and MP by 214% (both P<0.05) and there were no differences in the degree of reduction in either group. The magnitudes of reduction in CP and MP in both groups after DETC plus L-NAME were not different from those obtained when DETC was infused alone. The lower level of MP in the high salt rats suggested that oxidative stress was enhanced in this region as a consequence of the elevated sodium intake. Following the blockade of SOD, the raised level of superoxide anions in the kidney most probably mediated this vasoconstrictor action in the cortex and medulla. The observation that the magnitudes of the reductions in MP were unchanged when NO production was blocked suggested that NO was not involved and that the superoxide anions were acting directly on the vasculature.
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