Proceedings of The Physiological Society
University of Manchester (2010) Proc Physiol Soc 19, PC220
Consequences of blocking Superoxide Dismutase (SOD) on renal haemodynamics in functioning and blocked Angiotensin (Ang) system in rats
F. B. O'Connor2,1, A. F. Ahmeda1,2
1. Physiology Department, UCC, Cork, Ireland. 2. Physiology Department, UCC, Cork, Ireland.
Disruptions in the normal regulation of blood perfusion in the cortex and medulla can overpower the kidneys endogenous antioxidant system causing oxidative stress (OS). OS is a state in which the production of Reactive Oxygen Species (ROS) such as the superoxide anion (O2-) exceeds their metabolism. Ang ΙΙ like the O2- is a potent vasoconstrictor and both affect renal haemodynamics. This study was conducted to establish whether the increases in renal vascular tone which is caused by O2- could be changed by a dysfunctional Ang system in both normal and low salt (LS) fed rats. Four groups (n=6) of male Wistar rats fed a normal (0.3% Na+) or LS (0.03% Na+) diet, 250-300g, were anaesthetised with an I.P injection of 1 ml chloralose/urethane, 16.5/250 mg/ml. 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 and heart rate. The left kidney was exposed via a flank incision, placed in a holder and a small cannula inserted 4.5 mm into the corticomedullary border (CMB) for infusion of drugs at 1.0 ml/h. Two Laser-Doppler microprobes were inserted 1.5 and 5.0 mm into the kidney to measure cortical (CBP) and medullary (MBP) blood perfusion, respectively. After 2hrs, baseline values were taken then either diethyl-dithio-carbamate (DETC), a SOD inhibitor (4 mg/kg/min), or a combination of Losartan, AT1 receptor blocker (1mg/ml) plus DETC were infused into the CMB for 40 min. At the end of experiments the rats were killed by overdose of anesthetic. Data ± SEM were subjected to the Student′s t-test and significance taken at P<0.05. Baseline recordings for CBP and MBP in the normal rat were 88±15PU and 31±8PU versus 129±11PU in CBP and 40±6PU in MBP in the LS rat. Infusion of DETC in the normal rat decreased CBP and MBP by 18±5% and 20±5% respectively, both (P<0.05). In the LS group CBP decreased significantly by 16±4% while the reductions in MBP were not significant. The magnitude of reduction in CBP (15±4%) and MBP (7±9%) following combined infusion with Losartan + DETC (blocked Ang system) in the normal rat was less than the results obtained from the normal rat which received DETC only and the difference between them in the cortical region was significant. In the LS rat results recorded following combined infusion of Losartan + DETC showed a decrease in MBP by 9±8%, not significant and there was no change in CBP. Again the difference between the LS group that received DETC only was greater than the LS group receiving Losartan + DETC and the difference between them in the cortical region was significant. These results suggest that Ang ΙΙ modulate the effect of the DETC on renal microvasculature. They also indicate that manipulation of the Ang system may lead to positive reductions in vascular tone.
Where applicable, experiments conform with Society ethical requirements