Rahman Matlubur, Kimura Shoji, Yoneyama Hirohito, Kosaka Hiroaki, Fukui Toshiki, Nishiyama Akira, Abe Youichi
Department of Pharmacology, Kagawa Medical University, Japan.
Jpn J Pharmacol. 2002 Apr;88(4):436-41. doi: 10.1254/jjp.88.436.
The present study was conducted to determine whether exogenous angiotensin II (Ang II) may increase the renal interstitial fluid concentrations of NO2/NO3 (NOx) and cyclic guanosine monophosphate (cGMP) concomitantly and which Ang II receptor subtypes may induce these changes in anesthetized rats, using a microdialysis method. Ang II (50 ng/kg per min, i.v.) significantly increased mean blood pressure (MBP), extraction rates of renal interstitial NOx from 23.9+/-1.0 to 31.2+/-1.9 pmol/min, and cGMP from 4.1+/-0.3 to 6.4+/-0.5 fmol/min, and decreased renal blood flow (RBF). The AT1-receptor antagonist CV11974 alone significantly increased RBF, but did not alter MBP, renal interstitial concentrations of NOx and cGMP. A superimposition of Ang II on CV11974 did not affect MBP and RBF, but significantly increased renal interstitial concentrations of NOx and cGMP. The AT2-receptor antagonist PD123319 alone did not change any of the parameters. However, superimposition of Ang II on PD123319 increased MBP and decreased RBF without any effects on renal interstitial concentrations of NOx and cGMP. These results suggest that Ang II stimulates NO production via the AT2-receptor in the kidney.
本研究旨在使用微透析方法确定外源性血管紧张素II（Ang II）是否可同时增加肾间质液中NO2/NO3（NOx）和环磷酸鸟苷（cGMP）的浓度，以及哪种Ang II受体亚型可在麻醉大鼠中诱导这些变化。静脉注射Ang II（50 ng/kg每分钟）可显著升高平均血压（MBP），使肾间质NOx的提取率从23.9±1.0 pmol/分钟增加至31.2±1.9 pmol/分钟，cGMP从4.1±0.3 fmol/分钟增加至6.4±0.5 fmol/分钟，并降低肾血流量（RBF）。单独使用AT1受体拮抗剂CV11974可显著增加RBF，但不改变MBP、肾间质NOx和cGMP的浓度。在CV11974基础上叠加Ang II不影响MBP和RBF，但显著增加肾间质NOx和cGMP的浓度。单独使用AT2受体拮抗剂PD123319不改变任何参数。然而，在PD123319基础上叠加Ang II可升高MBP并降低RBF，但对肾间质NOx和cGMP的浓度无影响。这些结果表明，Ang II通过肾脏中的AT2受体刺激NO生成。
