Barry Elaine F, O'Neill Julie, Abdulla Mohammed H, Johns Edward J
Department of Physiology, University College Cork, Cork, Republic of Ireland.
Department of Gastroenterology, Mercy University Hospital, Cork, Republic of Ireland.
Clin Exp Pharmacol Physiol. 2021 Dec;48(12):1674-1684. doi: 10.1111/1440-1681.13570. Epub 2021 Aug 18.
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%), U V (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 U V 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.
本研究在高血压大鼠模型中探究了肾内输注血管紧张素1-7（Ang [1-7]）对肾脏排泄功能的影响。11周龄的自发性高血压大鼠（SHR，n = 7）和正常血压的Wistar大鼠（NCR，n = 7）用戊巴比妥钠（60 mg/kg腹腔注射）麻醉，并准备在肾间质输注Ang（1-7）（50 ng/分钟）期间测量平均动脉压（MAP）和左肾功能。收获肾脏，分离肾皮质和髓质，准备测量Ang II和Ang（1-7），并通过蛋白质免疫印迹法测定AT1和Mas受体蛋白表达。NCR组的MAP、肾小球滤过率（GFR）、尿流率（UF）和绝对钠排泄量（UNaV）分别为109 ± 16 mmHg、4.4 ± 1.0 mL/分钟/千克、102 ± 16 μL/分钟/千克和16 ± 3 μmol/分钟/千克，而SHR组分别为172 ± 24 mmHg、3.4 ± 0.7 mL/分钟/千克、58 ± 30 μL/分钟/千克和8.6 ± 4.8 μmol/分钟/千克。Ang（1-7）使NCR组的UF增加了31%、UNaV增加了50%、钠排泄分数（FENa）增加了22%（均p < 0.05），但对两组的GFR均无影响。SHR组中Ang（1-7）诱导的UF和UNaV增加幅度明显减弱（模型×药物，p < 0.05）。SHR组肾皮质的AT1:Mas受体表达比值显著更高（p < 0.05），但两组间肾脏Ang II和Ang（1-7）水平无统计学差异。在未受刺激的肾素-血管紧张素系统（RAS）背景下，SHR组中Ang（1-7）诱导的钠和水排泄增加受损。SHR肾脏对Ang（1-7）反应性的降低似乎与肾皮质中较高水平的AT1受体表达有关。
