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Intrarenal Mas and AT(1) receptors play a role in mediating the excretory actions of renal interstitial angiotensin-(1-7) infusion in anaesthetized rats
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Date
2017-09-21
Authors
O'Neill, Julie
Healy, Vincent
Johns, Edward J.
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John Wiley & Sons, Inc.
Published Version
Abstract
New Findings What is the central question of this study? Dietary sodium manipulation alters the magnitude of angiotensin‐(1–7) [Ang‐(1–7)]‐induced natriuresis. The present study sought to determine whether this was related to relative changes in the activity of intrarenal Mas and/or AT1 receptors. What is the main finding and its importance? Angiotensin‐(1–7)‐induced diuresis and natriuresis is mediated by intrarenal Mas receptors. However, intrarenal AT1 receptor blockade also had an inhibitory effect on Ang‐(1–7)‐induced natriuresis and diuresis. Thus, Ang‐(1–7)‐induced increases in sodium and water excretion are dependent upon functional Mas and AT1 receptors. We investigated whether angiotensin‐(1–7) [Ang‐(1–7)]‐induced renal haemodynamic and excretory actions were solely dependent upon intrarenal Mas receptor activation or required functional angiotensin II type 1 (AT1) receptors. The renin–angiotensin system was enhanced in anaesthetized rats by prior manipulation of dietary sodium intake. Angiotensin‐(1–7) and AT1 and Mas receptor antagonists were infused into the kidney at the corticomedullary border. Mas receptor expression was measured in the kidney. Mean arterial pressure, urine flow and fractional sodium excretion were 93 ± 4 mmHg, 46.1 ± 15.7 μl min−1 kg−1 and 1.4 ± 0.3%, respectively, in the normal‐sodium group and 91 ± 2 mmHg, 19.1 ± 3.3 μl min−1 kg−1 and 0.7 ± 0.2%, respectively, in the low‐sodium group. Angiotensin‐(1–7) infusion had no effect on mean arterial pressure in rats receiving a normal‐sodium diet but decreased it by 4 ± 5% in rats receiving a low‐sodium diet (P < 0.05). Interstitial Ang‐(1–7) infusion increased urine flow twofold and fractional sodium excretion threefold (P < 0.05) in rats receiving a normal‐sodium diet and to a greater extent, approximately three‐ and fourfold, respectively, in rats receiving the low‐sodium diet (both P < 0.05). Angiotensin‐(1–7)‐induced increases in urine flow and fractional sodium excretion were absent in both dietary groups during intrarenal AT1 or Mas receptor inhibition after either losartan or A‐779, respectively. Thus, AT1 receptor activation, as well as Mas receptor activation, plays an essential role in mediating Ang‐(1–7)‐induced natriuresis and diuresis. Whether this is because Ang‐(1–7) partly antagonizes AT1 receptors or whether Ang‐(1–7)‐induced natriuresis is mediated through AT1–Mas receptor dimerization remains unclear.
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Keywords
II Type-1 receptor , Natriuretic action , Converting enzyme , Hypertensive rats , Ace inhibition , Responses , Antagonist , Blockade , Ligand , Cortex
Citation
O'Neill, J., Healy, V., Johns, E. J. (2017) 'Intrarenal Mas and AT(1) receptors play a role in mediating the excretory actions of renal interstitial angiotensin-(1-7) infusion in anaesthetized rats', Experimental Physiology, 102, pp. 1700-1715. doi:10.1113/EP086513
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© 2017, The Authors. Experimental Physiology ©2017 The Physiological Society. This is the peer reviewed version of the following article: O'Neill, Julie; Healy, Vincent; Johns, Edward J. (2017) 'Intrarenal Mas and AT(1) receptors play a role in mediating the excretory actions of renal interstitial angiotensin-(1-7) infusion in anaesthetized rats'. Experimental Physiology, 102 :1700-1715. doi:10.1113/EP086513, which has been published in final form at doi:10.1113/EP086513. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.