Intrarenal Mas and AT 1 receptors play a role in mediating the excretory actions of renal interstitial angiotensin-(1-7) infusion in anaesthetized rats

• Published in: Experimental physiology Vol. 102; no. 12; pp. 1700 - 1715
• Main Authors: O'Neill, Julie, Healy, Vincent, Johns, Edward J
• Format: Journal Article
• Language: English
• Published: England 01-12-2017
• Subjects: Anesthesia, General; Angiotensin I - administration & dosage; Angiotensin II - administration & dosage; Angiotensin II - analogs & derivatives; Angiotensin II Type 1 Receptor Blockers - administration & dosage; Animals; Diet, Sodium-Restricted; Glomerular Filtration Rate - drug effects; Hemodynamics - drug effects; Infusions, Parenteral; Kidney - blood supply; Kidney - drug effects; Kidney - metabolism; Losartan - administration & dosage; Male; Natriuresis - drug effects; Peptide Fragments - administration & dosage; Proto-Oncogene Proteins - agonists; Proto-Oncogene Proteins - metabolism; Rats, Wistar; Receptor, Angiotensin, Type 1 - agonists; Receptor, Angiotensin, Type 1 - metabolism; Receptors, G-Protein-Coupled - agonists; Receptors, G-Protein-Coupled - metabolism; Renal Circulation - drug effects; Renal Elimination - drug effects; Renin-Angiotensin System - drug effects; Signal Transduction; Sodium, Dietary - administration & dosage; intrarenal AT1 and Mas receptors; natriuresis; dietary sodium
• ISSN: 0958-0670; 1469-445X
• DOI: 10.1113/EP086513

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 AT
receptors. What is the main finding and its importance? Angiotensin-(1-7)-induced diuresis and natriuresis is mediated by intrarenal Mas receptors. However, intrarenal AT
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 AT
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 (AT
) receptors. The renin-angiotensin system was enhanced in anaesthetized rats by prior manipulation of dietary sodium intake. Angiotensin-(1-7) and AT
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
 kg
and 1.4 ± 0.3%, respectively, in the normal-sodium group and 91 ± 2 mmHg, 19.1 ± 3.3 μl min
 kg
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 AT
or Mas receptor inhibition after either losartan or A-779, respectively. Thus, AT
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 AT
receptors or whether Ang-(1-7)-induced natriuresis is mediated through AT
-Mas receptor dimerization remains unclear.