Proceedings of The Physiological Society
University of Oxford (2011) Proc Physiol Soc 23, PC279
The role of Angiotensin (1-7) in the regulation of renal haemodynamics
J. O Neill1, N. Mc Conigley1, E. J. Johns1
1. Physiology, University College Cork, Cork, Ireland.
The Renin Angiotensin System (RAS) is a powerful endogenous hormonal cascade that is involved in the maintenance of renal, cardiovascular and extracellular fluid volume homeostasis via the potent vasoconstrictor, Angiotensin II (Ang II). Recently, it has emerged that a second Angiotensin Converting Enzyme (ACE) isoform, ACE 2 acts upon Ang II to generate Ang (1-7), a vasodilator with natriuretic and diuretic actions at the kidney that directly oppose those of Ang II. Currently, the precise way in which Ang (1-7) influences renal hemodynamics is unclear. Thus, the aim of this study was to determine whether Ang (1-7) would increase renal blood flow (RBF) and whether these affects were solely dependent upon Mas receptor activation or whether simultaneous Ang II induced AT 1 receptor stimulation was required. Groups of (n=4-8) male Wistar rats were anaesthetized (i.p. 1.2ml chloralose/urethane, 16.5/250mg/ml) and prepared for measurement of mean arterial blood pressure (MAP) and RBF, the intravenous infusion of saline at 3ml/h and the corticomedullary infusion of drugs at 1.0ml/h. Increasing doses of Ang (1-7) (9x10-10M; 3x10-9M; 9x10-9M; 2.7x10-8M) were infused into group 1 rats in a random order. Losartan (AT1 anatagonist: 3x10-6M) and A-779 (Mas antagonist: 3X10-7M) were co-infused into Group 2 and 3 rats, respectively along with previously mentioned doses of Ang (1-7). Anaesthetic (0.05 ml) was administered intravenously every 30 mins throughout the experiment. The duration of the experiment was approximately 4 hours after which animals were killed using anaesthetic overdose. Data±SEM were subjected to a one way ANOVA and significance taken when P<0.05. Baseline MAP was between 73±4 and 87±3.6mmHg across all groups. RBF was between 3.8±1 and 4.6±0.7 ml/min across all groups at baseline. Ang (1-7) (9x10-10 M and 3X10-9M) increased RBF by 16% and 20% respectively (both P<0.05). The co-infusion of Losartan blunted these responses by 31% and 77%, respectively. Similarly, A-779 reduced the magnitude of the response to Ang (1-7) (9x10-10 M and 3x10-9 M) by 48% and 55% respectively. These results suggest that optimum doses of Ang (1-7) (9x10-10 M and 3X10-9M) increase RBF, indicating possible dilation at the level of the afferent arteriole. The two higher doses of Ang (1-7) (9x10-9 M and 2.7x10-10 M) failed to produce any meaningful changes in RBF, indicating a biphasic affect and possible Mas receptor saturation. Ang (1-7) induced increases in RBF were reduced by A-779 and this would certainly suggest that the dilatory action of Ang (1-7) is mediated, in part, by the Mas receptor. However, Losartan also blunted these responses and this may indicate that an interaction between the AT1 and Mas receptors is required to fully mediate the actions of Ang (1-7).
Where applicable, experiments conform with Society ethical requirements