Proceedings of The Physiological Society
University of Manchester (2010) Proc Physiol Soc 19, PC251
Impact of dietary sodium on the renal haemodynamic and excretory responses to Angiotensin 1-7 in anaesthetised Rats.
J. O'Neill1, E. J. Johns1
1. Department of Physiology, University College Cork, Cork, Ireland.
The renin angiotensin system (RAS) is a hormonal cascade involved in renal and cardiovascular homeostasis. A second isoform of angiotensin converting enzyme (ACE 2) has been identified which produces the vasodilator peptide Ang1-7 that has natriuretic and diuretic actions. Our previous studies reported that the renal actions of Ang1-7 were augmented in rats exposed to a low sodium (Na) diet (Corbett and Johns 2009). The hypotheses tested herein was that suppression of the endogenous RAS, by placing rats on a high Na diet, would blunt the renal haemodynamic and excretory actions of Ang 1-7. Groups (n=8) of male Wistar rats (250-300g) were fed a normal (0.3%Na ) or high Na (3% Na ) diet for 2 weeks. Anaesthesia was induced using 1.2 ml chloralose/urethane IP. Cannulae were placed in a femoral artery, to monitor mean arterial pressure (MAP), and vein, for infusion of saline (0.9g/l NaCl) containing FITC inulin (2g/l) at 3ml/h. The left kidney was exposed via a flank incision, its ureter cannulated for urine collection and a small cannula inserted 4.0-4.5 mm into the cortico-medullary border for the infusion of saline and Ang 1-7 at a concentration of 9x10-7M or 3x10-6M at 1 ml/h. After 1.5h stabilization, four 20 min clearances were taken, two before and two 45 min after the start of Ang1-7 infusion. The animals were killed at the end of the experiment. Data, means±SEM were subjected to a two way Anova and significance taken at P<0.05. The control values for MAP, urine volume (UV), absolute sodium excretion (UVNa) and fractional sodium excretion (FENa) were similar in all groups and averaged 91±4mmHg, 31±9μl/min, 4±1μmol/min and 1.0±0.4% while glomerular filtration rate (GFR) was lower (P<0.05) in the group which received a normal diet and a low dose of Ang (1-7), 2.0±0.2ml/min/Kg vs 3.0±0.4ml/min/Kg. MAP was significantly (both P<0.05) decreased by the high dose Ang (1-7) by 6% in normal Na fed rats and by 5% in the high Na fed rats. The low dose of Ang (1-7) significantly (P<0.05) increased GFR in the high Na fed rats, by 18%. Infusion of Ang (1-7) at the low and high doses increased UV by 100% and 150%, UVNa by 133% and 200% and FENa by 100% and 300% respectively (all P<0.05) in normal Na fed rats. The high Na diet blunted the magnitude of all excretory responses, UV by 76% and 82% (P<0.05), UVNa by 91% and 100% (P<0.05) and FENa by 95% (P<0.05) and 257% (P<0.05) following infusion of both the low dose and high doses of Ang (1-7), respectively. The findings show that the low, but not high, dose of Ang1-7 induced a small rise in GFR and dose related increases in FENa suggested Ang1-7 has direct tubular actions. The blunted renal excretory responses to Ang1-7 in the high Na fed rats provides further evidence that the level of endogenous RAS activity can determine the renal actions of Ang1-7.
Where applicable, experiments conform with Society ethical requirements