The renal functional responses to Angiotensin 1-7 in the DOCA salt hypertensive rat

37th Congress of IUPS (Birmingham, UK) (2013) Proc 37th IUPS, PCC336

Poster Communications: The renal functional responses to Angiotensin 1-7 in the DOCA salt hypertensive rat

E. Barry1, E. J. Johns1

1. Department of Physiology, University College Cork, Cork, Ireland.

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Angiotensin 1-7 (Ang1-7) has diuretic/natriuretic properties at the kidney. There is evidence that this response is due to a counter-regulation of the anti-diuretic/anti-natriuretic actions of Angiotensin II and is therefore dependant on the level of activation or suppression of the endogenous renin-angiotensin system (RAS). This study investigated whether the excretory responses to intrarenal Ang1-7 are altered in Deoxycorticosterone Acetate (DOCA) salt hypertensive rats where the RAS is known to be depressed. Male Wistar rats received two s.c. injections weekly of DOCA(15mg/kg) in arachis oil (2ml/kg) and 9% NaCl/2% KCl drinking water for four weeks, one week following unilateral nephrectomy performed under 5% isoflurane (0.5L/min O2) induction/2% (0.2L/min O2) maintenance. Prior to the terminal experiments animals were placed in metabolic cages to determine baseline excretory function. Anaesthesia was induced using 1ml/kg body weight sodium pentobarbital i.p. The femoral artery was cannulated, to monitor mean arterial pressure (MAP), and vein, for infusion of saline at 3ml/h containing inulin. The left ureter was cannulated for urine collection and a small cannula inserted into the cortico-medullary border for the infusion of saline and Ang1-7 (6×10-6M) at 1 ml/h. After 1.5h, 20 min clearances were taken, two before and two 50 mins after the start of the Ang1-7 infusion. The rats were killed at the end of the experiment by anaesthetic overdose. Data, means±SEM were subjected to t-tests and significance taken at P<0.05. DOCA treated group (n=6) had a higher GFR than the control group (n=7), at 3.3±0.2 vs. 1.1±0.06ml/min/kg respectively, and a higher urine volume (UV), at 131.5±11.1 vs. 29.5±3.6µl/min respectively. Sodium excretion values were also higher for the DOCA treated group compared to the control group, with absolute sodium excretion (UVNa) values of 29.0±2.1 vs. 1.42±0.09 µmol/min respectively, and fractional sodium excretion values(FENa) of 5.4±0.4 vs. 0.9±0.05% respectively. Ang1-7 had no effect on blood pressure, at 111±5 mmHg for control rats and 162±4 mmHg for DOCA rats, or GFR, at 4.4±0.4ml/min/kg and following Ang1-7 infusion 5.2±0.5ml/min/kg for control rats and for DOCA rats 9.1±2.2ml/min/kg and 10.9±2.8ml/min/kg before and after infusion respectively. In control rats, UV significantly increased (P<0.05) from 100.9±6.9 to 139.1±4.5 µl/min, UVNa, from 16.0±1.3 to 24.3±1.0 µmol/min and FENa by 2.3±0.5 to 2.9±0.5%. In the DOCA model these responses to Ang1-7 were completely blunted, with UV, 163.5±35.7µl/min, UVNa, 39±11µmol/min and FeNa, 2.4±0.07% and following Ang1-7 infusion UV, 145.4±47.7µl/min, UVNa, 29.4±8.5µmol/min, and FENa, 1.5±0.2%. These findings suggest that the suppression of the RAS in the DOCA model of hypertension interferes with the diuretic/natriuretic response seen in normal animals to intra renal Ang1-7 infusion.



Where applicable, experiments conform with Society ethical requirements.

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