Patzak Andreas, Lai En Y, Mrowka Ralf, Steege Andreas, Persson Pontus B, Persson A Erik G
Institute of Physiology, Humboldt-University of Berlin, University Hospital Charité, Berlin, Germany.
Kidney Int. 2004 Nov;66(5):1949-58. doi: 10.1111/j.1523-1755.2004.00981.x.
Recent studies have indicated that angiotensin II (Ang II) possibly activates the nitric oxide (NO) system. We investigated the role of AT receptor subtypes (AT-R) in mediating the Ang II-induced NO release in afferent arterioles (Af) of mice.
Isolated Af of mice were perfused, and the isotonic contraction measured. Further, NO release was determined using DAF-FM, a fluorescence indicator for NO. Moreover, we qualitatively assessed the expression of AT-R at the mRNA level using reverse transcription-polymerase chain reaction (RT-PCR).
Ang II reduced luminal diameters dose dependently (67.3 +/- 6.3% at 10(-6) mol/L). Inhibition of AT2-R with PD123.319 did not change the Ang II contractile response. AT1-R blockade with ZD7155 inhibited contraction. Stimulation of AT2-R during AT1-R inhibition with ZD7155, and preconstriction with norepinephrine (NE) had no influence on the diameter. Drug application via the perfusion pipette changed flow and pressure, and enhanced NO fluorescence by DeltaF = 4.0 +/- 0.4% (N= 14, background). Luminal application of Ang II (10(-7) mol/L) increased the NO fluorescence by DeltaF = 9.9 +/- 1.2% (N= 8). AT1-R blockade blunted the increase to background levels (DeltaF to 4.0 +/- 0.3%, N= 6, P < 0.05), but AT2-R blockade did not (8.1 +/- 0.9%, N= 9). L-NAME nearly abolished the Ang II effect on the NO fluorescence (DeltaF = 1.6 +/- 0.5% (N= 8). NE did not increase NO release beyond the background levels. RT-PCR showed expression of both AT1-R and AT2-R.
The results indicate an Ang II-induced NO release in Af of mice, which is mediated by AT1-R. Thus, Ang II balances its own constrictor action in Af. This control mechanism is very important in view of high renin and angiotensin II concentration in the juxtaglomerular apparatus.
近期研究表明，血管紧张素II（Ang II）可能激活一氧化氮（NO）系统。我们研究了AT受体亚型（AT-R）在介导Ang II诱导的小鼠传入小动脉（Af）中NO释放的作用。
对分离的小鼠Af进行灌注，并测量等渗收缩。此外，使用DAF-FM（一种NO荧光指示剂）测定NO释放。此外，我们使用逆转录-聚合酶链反应（RT-PCR）在mRNA水平定性评估AT-R的表达。
Ang II剂量依赖性地减小管腔直径（10⁻⁶mol/L时为67.3±6.3%）。用PD123.319抑制AT2-R不会改变Ang II的收缩反应。用ZD7155阻断AT1-R可抑制收缩。在用ZD7155抑制AT1-R期间刺激AT2-R以及用去甲肾上腺素（NE）预收缩对直径没有影响。通过灌注移液管给药会改变流量和压力，并使NO荧光增强ΔF = 4.0±0.4%（N = 14，背景值）。管腔内应用Ang II（10⁻⁷mol/L）使NO荧光增加ΔF = 9.9±1.2%（N = 8）。阻断AT1-R可使增加幅度降至背景水平（ΔF降至4.0±0.3%，N = 6，P < 0.05），但阻断AT2-R则不会（8.1±0.9%，N = 9）。L-NAME几乎消除了Ang II对NO荧光的影响（ΔF = 1.6±0.5%（N = 8）。NE不会使NO释放增加超过背景水平。RT-PCR显示AT1-R和AT2-R均有表达。
结果表明Ang II可诱导小鼠Af中NO释放，这是由AT1-R介导的。因此，Ang II在Af中平衡其自身的收缩作用。鉴于近球小体中肾素和血管紧张素II浓度较高，这种控制机制非常重要。
