The renin angiotensin system (RAS) is involved in the regulation of renal function and cardiovascular homeostasis. The actions of the vasoconstrictor and anti-natriuretic factor angiotensin II (Ang II) are well described, however, recently the discovery of a second isoform of angiotensin converting enzyme which generates angiotensin 1-7 (Ang1-7) has generated further interest in this peptide. Studies to date suggest that Ang1-7 opposes the effects of Ang II, that is it is vasodilator and has diuretic properties. This study investigated the effects of Ang 1-7 on regional renal haemodynamics in animals of different dietary sodium intakes to stimulate or suppress the endogenous RAS. Three groups (n=6), 250-300g, of male Wistar rats fed a normal salt (NS) [0.3% Na+], high salt (HS) to suppress the RAS [3% Na+], or low salt (LS) to stimulate the RAS [0.03% Na+] diet for three weeks, were anaesthetised with 1 ml i.p. chloralose/urethane (16.5/250 mg/ml, respectively). The right femoral vein and artery were cannulated for infusion of saline (154 mM NaCl) at 3 ml/h, anaesthetic supplementation (0.05 ml every 30 min), and measurement of arterial blood pressure and heart rate. The left kidney was exposed via a flank incision, placed in a holder and a small cannula was inserted 4.5 mm into the corticomedullary border (CMB) for infusion of saline or Ang1-7 at 1.0 ml/h. Two Laser-Doppler microprobes were inserted 1.5 and 4.0 mm into the kidney to measure cortical (CP) and medullary (MP) blood perfusion. 90 minutes were allowed for recovery from the surgery followed by baseline recording, and then infusion of the Ang (1-7) at two different doses (low, 15ng/min and high, 50ng/min) into the CMB for 40 min. At the end of experiments the rats were killed with an overdose of anaesthetic. Data, presented as mean ± SEM, were subjected to the Student′s t-test and significance taken at P<0.05. Baseline recordings for CP and MP in NS were 227±50PU and 98±12PU, in HS were 313±48PU and 132±20PU and in LS were 293±40PU and 123±9PU, respectively. Infusion of Ang 1-7 at low and high doses increased CP in all groups (15±5% and 7±3% in NS, 9±2% and 18±10% in HS, and 9±2 and 1±3% in LS; P<0.05). MP increased significantly (P<0.05) only following the infusion of the low dose on both normal and high salt fed rats by 10± 3% and 8±3%, respectively. In LS group, where RAS is activated and Ang II is at a high level, the MP remained unchanged at both doses. These results indicate that Ang 1-7 caused a vasodilatory effect on the renal microvasculature, expressed as an increase in blood perfusion, which was much more evident in the cortical region but could not be related to the level of dietary sodium intake. Ang 1-7 caused a similar vasodilation in the medullary region except when the RAS was suppressed by the high salt intake when no effect could be demonstrated.
37th Congress of IUPS (Birmingham, UK) (2013) Proc 37th IUPS, PCD219
Poster Communications: The effects of Angiotensin 1-7 on renal haemodynamics
W. E. Osman1, E. J. Johns1, A. F. Ahmeda1
1. Physiology Department, UCC, Cork, Ireland.
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Where applicable, experiments conform with Society ethical requirements.