Conference Contribution Details
Mandatory Fields
Johns, E;
Renal Haemodynamics: mechanisms to understand disease
FASEB Summer Research Conference
Vermont Academy, Vermont, USA
Conference Organising Committee Chairperson
2010
()
Optional Fields
19-JUN-10
23-JUN-10

Impact of Angiotensin1-7 (Ang1-7) on renal haemodynamic and excretory function on manipulation of dietary sodium intake in the rat

The renin angiotensin system (RAS) is 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 and appears to buffer the vasoconstrictor and antinatriuretic actions of AngII.  The hypotheses tested herein was that activation or suppression of the endogenous RAS, by placing rats on a low or high Na diet, would enhance or blunt the renal haemodynamic and excretory actions of Ang 1-7.

 

Groups (n=5-8) of male Wistar rats (250-300g) were fed a low (0.03%), 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 at 3ml/h containing inulin. The left kidney was exposed, 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, four 20 min clearances were taken, two before and two 45 min after the start of Ang1-7 infusion. Data, means±SEM were subjected to Anova and significance taken at P<0.05.  

 

Basal values for MAP, glomerular filtration rate (GFR), and urine flow (UV) and fractional sodium excretion (FENa) were similar in all groups and averaged 92±3 mmHg, 2.50±0.15 ml/min/kg, 21.9±2.1 ml/min/kg and 1.45±0.32%.  MAP was unchanged during the infusion of both doses of Ang1-7 in the low Na diet rats but was decreased (both P<0.05) 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) increased (P<0.05) GFR in low and high Na fed rats, by some 20%. 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. In the rats on a low sodium diet, both doses of Ang1-7 increased (all P<0.05) GFR by some 30%, UV by 200% and FENa by three fold, which were greater (P<0.05) in magnitude than the responses in the rats on a normal Na intake.  The high Na diet blunted the magnitude of all excretory responses, UV by 80% (P<0.05), UVNa by 95% (P<0.05) and FENa by 95% (P<0.05) following infusion of Ang (1-7).

 

Ang 1-7 infusion caused dose related diuretic and natriuretic responses in the rats on a normal sodium intake which indicated a tubular action.  The excretory responses to Ang1-7 were markedly enhanced in the low Na rats but suppressed in the high Na rats.  The underlying mechanisms are unclear but may reside in alterations in AT1 and/or mas receptor density or ACE2 activity.

FASEB