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Corbett, A and Johns, E;
Physiological Society General Meeting
The impact of a low sodium diet on the renal functional responses to angiotension 1-7 (Ang1-7) in anaesthetised rats
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Angiotension converting enzyme isoform 2 (ACE2) converts angiotensin II (AngII) into Ang1-7 which has vasodilator and natriuretic and diuretic actions at the kidney. Burgelova et al (2005) reported that the influence of Ang1-7 on renal haemodynamic and excretory function was enhanced in rat models of hypertension in which plasma renin activity was elevated. This study examined whether activation of the endogenous renin-angiotension system, by placing animals on a low sodium diet, would enhance the haemodynamic and excretory actions of Ang1-7 at the kidney. Groups (n=5 or 6) of male Wister rats (220-300g) were maintained on a normal (0.3% Na+) or a low sodium (0.03% Na+) diet for 2 weeks. Following anaesthesia, 1ml chloralose/urethane (16.5/250 mg/ml) i.p., cannulae were placed in a femoral artery, to monitor mean arterial pressure (MAP) and vein, to allow infusion of saline (0.9g/l NaCl) containing inulin (2g/l) at 3ml/h. The left kidney was exposed via the flank, its ureter cannulated for urine collection, the renal artery cleared to fitf an ultrasonic flow probe to measure renal blood flow (RBF), and a small cannula was inserted 4.0 to 4.5 mm into the cortex to lie at the cortico-medullary boarder and saline infused at 1 ml/h. Afterg a 2h stabilisation period, four 20 min clearances were performed, two before and two 30 min after starting an infusion of Ang1-7 at a concentration of either 9x10-7 M or 3x10-6M. Data, means±S.E.M., were deemed significant when P<0.05 (Wilcoxon Signed Rank Test). Control values for MAP, glomerular filtration rate (GFR), RBF and urine flow (UV) were similar in all groups at 92±3 mmHg, 2.50±0.15 ml/min/kg, 4.5±0.5 ml/min and 21.9±2.1 μl/min/kg while fractional sodium excretion (FENa) was reduced (P<0.05) in the low sodium diet group, 0.75±0.14 versus 1.45±0.32%. Infusion of Ang1-7 at 9x10-7 and 3x10-6 M increased GFR by 20% and 28%, UV by 23% and 71% and FENa by 25% and 95%, respectively (all P<0.05) in rats on a normal sodium diet. In the rats on a low sodium diet, both doses of Ang1-7 increased (all P<0.05) GFR by 45% and 31%, UV by 200% and 225% and FENa of 350 and 320%, respectively, which were larger (P<0.05) than the responses in the rats on a normal sodium intake. Ang1-7 has vasodilator properties, as it raised GFR but this was not related to the dose of peptide infused or the dietary sodium status. By contrast, in rats on a normal sodium intake, the diuretic and natriuretic responses to Ang1-7 were dose related suggesting a tubular action. Interestingly, the excretory responses to Ang1-7 were markedly enhanced in rats on the low sodium diet and appeared maximal as a dose-response relationship was not evident. These findings demonstrate that manipulation of dietary sodium intake impacts on the ability of Ang1-7 to determine sodium excretion.

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