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New Findings: What is the central question of this study?Are renal functional responses to intrarenal angiotensin 1–7 (Ang (1–7)) infusion dependent on the level of the endogenous renin–angiotensin system (RAS) in the two‐kidney one‐clip (2K1C) and deoxycorticosterone acetate (DOCA)‐salt animal models of hypertension?What is the main finding and its importance?The renal actions of Ang (1–7) are dependent on the relative endogenous levels of each arm of the classical angiotensin II–angiotensin II type 1 receptor (AT1R) axis and those of the Ang (1–7)–Mas receptor axis. These findings support the hypothesis that a balance exists between the intrarenal classical and novel arms of the RAS, and in particular the relative abundance of AT1R to Mas receptor, which may to a large extent determine the renal excretory response to Ang (1–7) infusion. This study investigated the action of angiotensin 1–7 (Ang (1–7)) on renal haemodynamic and excretory function in the two‐kidney one‐clip (2K1C) and deoxycorticosterone acetate (DOCA)‐salt rat models of hypertension, in which the endogenous renin–angiotensin system (RAS) activity was likely to be raised or lowered, respectively. Rats were anaesthetised and prepared for the measurement of mean arterial pressure and kidney function during renal interstitial infusion of Ang (1–7) or saline. Kidney tissue concentrations of angiotensin II (Ang II) and Ang (1–7) were determined. Intrarenal infusion of Ang (1–7) into the clipped kidney of 2K1C rats increased urine flow (UV), absolute (UNaV) and fractional sodium (FENa) excretions by 110%, 214% and 147%, respectively. Renal Ang II concentrations of the clipped kidney were increased with no major changes in Ang (1–7) concentration. By contrast, Ang (1–7) infusion decreased UV, UNaV, and FENa by 27%, 24% and 21%, respectively in the non‐clipped kidney in which tissue Ang (1–7) concentrations were increased, but renal Ang II concentrations were unchanged compared to sham animals. Ang (1–7) infusion in DOCA‐salt rats had minimal effects on glomerular filtration rate but significantly decreased UV, UNaV and FENa by ∼30%. Renal Ang (1–7) concentrations were higher and Ang II concentrations were lower in DOCA‐salt rats compared to sham rats. These findings demonstrate that the intrarenal infusion of exogenous Ang (1–7) elicits different renal excretory responses the magnitude of which is dependent on the balance between the endogenous renal Ang II–AT1 receptor axis and Ang (1–7)–Mas receptor axis. [ABSTRACT FROM AUTHOR]

This study investigated the impact of intrarenal angiotensin 1–7 (Ang [1–7]) infusion on renal excretory function in a rat model of hypertension. Eleven‐week‐old spontaneously hypertensive rats (SHRs, n = 7) and Han Wistar controls (NCR, n = 7) were anaesthetised with sodium pentobarbital (60 mg/kg i.p.) and prepared for the measurement of mean arterial pressure (MAP) and left renal function during renal interstitial infusion of Ang (1–7) (50 ng/min). The kidneys were harvested, the renal cortex and medulla separated, prepared for measurement of Ang II and Ang (1–7) and Western blot determination of AT1 and Mas receptor protein expression. MAP, glomerular filtration rate (GFR), urine flow (UF) and absolute sodium excretion (UNaV) were 109 ± 16 mmHg, 4.4 ± 1.0 mL/min/kg, 102 ± 16 µL/min/kg and 16 ± 3 µmol/min/kg, respectively in the NCR and 172 ± 24 mmHg, 3.4 ± 0.7 mL/min/kg, 58 ± 30 μL/min/kg and 8.6 ± 4.8 μmol/min/kg respectively in the SHR. Ang (1–7) increased UF (31%), UNaV (50%) and fractional sodium excretion (FENa+) (22%) in the NCR group (all p < 0.05) but had no effect on GFR in either group. The magnitudes of the Ang (1–7)‐induced increases in UF and UNaV were significantly blunted in the SHR group (model × drug p < 0.05). The renal cortical AT1: Mas receptor expression ratio was significantly higher in the SHR group (p < 0.05) but renal Ang II and Ang (1–7) levels were not statistically different between groups. The Ang (1–7)‐induced increases in sodium and water excretion were impaired in the SHR group in the context of an unstimulated RAS. The decrease in responsiveness of the SHR kidney to Ang (1–7) appears to be associated with higher levels of AT1 receptor expression in the renal cortex. [ABSTRACT FROM AUTHOR]