Conference Publication Details
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JohnsE and Albulushi, A;
Physiological Society General Meeting
Impact of Angiotensin 1-7 (Ang1-7) on renal haemodynamic and excretory function anaesthetised normotensive and hypertensive rats.
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Increasingly, it is perceived that Ang1-7 has significant physiological actions at the vascular and tubular levels of the kidney which are generally opposite to those of angiotensin II (AngII). Recent reports have shown Ang1-7 to cause a renal vasodilation and a diuresis and natriuresis and that these actions were enhanced in transgenic and renovascular models of hypertension (Burgelova et al, 2005) and concluded that the response to the peptide was related to the degree of activation of the renin-angiotensin system. This study tested the hypothesis that the renal haemodynamic and excretory responses to Ang1-7 would be greater in the spontaneously hypertensive rat (SHR) than normotensive rats. Male Wistar and SHR (300-350 g) were anaesthetised with 1 ml i.p. chloralose/urethane (16.5/250mg/ml) and cannulae placed in a femoral artery to measure blood pressure and and vein for the infusion of saline (9g/l NaCl) at 3 ml/h. The left kidney was exposed, its ureter cannulated, an ultrasonic flow probe placed on the renal artery and a small cannula inserted 4.5 mm into the kidney for infusion of saline/vehicle or Ang1-7 at 1.0ml/h intra-renally (i.r.) at the cortico-medullary boarder. Following a 1-2 h recovery, four 20 min clearances were taken, 2 before and 2 during the intrarenal infusion of saline or Ang1-7 (3x10-7 M). Data, means S.E.M, were deemed significant when P<0.05 (Wilcoxon Signed Rank Test). Infusion of saline i.r. in Wistar rats (n=5) had no effect on blood pressure (BP), renal blood flow (RBF), glomerular filtration rate (GFR), urine flow (UV), absolute (UNaV) or fractional sodium excretion (FENa). In the Wistar group in which Ang1-7 was infused i.r. (n=5), BP, at 925 mmHg, RBF, at 1.660.16 ml/min and GFR, at 2.710.21 ml/min/kg, were unchanged but UV, at 19.73.8 μl/min/kg, UNa, at 0.290.11μmol/min/kg, and FENa, at 0.690.27%, were increased (both P<0.05) by 2 to 2.5 fold. Infusion of Ang1-7 i.r. in the SHR (n=7) had no effect on either BP or RBF but increased UV, UNaV and FENa by between 2 and 3 fold (all P<0.05), respectively, which were responses very similar to those obtained in the Wistar rats. These findings demonstrated that infusion of Ang1-7 locally into the kidney at this dose, had minimal effects on renal haemodynamics but caused a marked increase in both water and sodium excretion. This would suggest that the peptide was having a direct action on tubular reabsorptive processes. Surprisingly, the magnitude of the excretory responses in the SHR were similar to those of the Wistar and did not support the proposed hypothesis. One possible reason may be due to the relatively normal levels of plasma renin activity reported to be present in the SHR (Bivol et al, 2007).

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