Thorup C, Kornfeld M, Winaver J M, Goligorsky M S, Moore L C
Department of Physiology, Göteborg University, S-41390 Göteborg, Sweden.
Pflugers Arch. 1998 Feb;435(3):432-4. doi: 10.1007/s004240050535.
Nitric oxide (NO) has been implicated as a modulator of the vascular effects of angiotensin II (ANG II) in the kidney. We used a NO-sensitive microelectrode to study the effect of ANG II on NO release, and to determine the effect of selective inhibition of the ANG II subtype I receptor (AT1) with losartan (LOS) and candesartan (CAN). NO release from isolated and perfused renal resistance arteries was measured with a porphyrin-electroplated, carbon fiber. The vessels were microdissected from isolated perfused rat kidneys and perfused at constant flow and pressure in vitro. The NO-electrode was placed inside the glass collection cannula to measure vessel effluent NO concentration. ANG II stimulated NO release in a dose-dependent fashion: 0.1 nM, 10 nM and 1000 nM ANG II increased NO-oxidation current by 85+/-18 pA (n = 11), 148+/-22 pA (n = 11), and 193+/-29 pA (n = 11), respectively. These currents correspond to changes in effluent NO concentration of 3.4+/-0.5 nM, 6.1+/-1.1 nM, and 8.2+/-1.3 nM, respectively. Neither LOS (1 muM) nor CAN (1 nM) significantly affected basal NO production, but both AT1-receptor blockers markedly blunted NO release in response to ANG II (10 nM): 77+/-6% inhibition with LOS (n = 8) and 63+/-9% with CAN (n = 8). These results are the first to demonstrate that ANG II stimulates NO release in isolated renal resistance arteries, and that ANG II-induced NO release is blunted by simultaneous AT1-receptor blockade. Our findings suggest that endothelium-dependent modulation of ANG II-induced vasoconstriction in renal resistance arteries is mediated, at least in part, by AT1-receptor-dependent NO release.
一氧化氮（NO）被认为是肾脏中血管紧张素II（ANG II）血管效应的调节剂。我们使用对NO敏感的微电极来研究ANG II对NO释放的影响，并确定用氯沙坦（LOS）和坎地沙坦（CAN）选择性抑制ANG II I型受体（AT1）的效果。用卟啉电镀的碳纤维测量分离并灌注的肾阻力动脉中的NO释放。血管从分离灌注的大鼠肾脏中显微解剖出来，并在体外以恒定流量和压力进行灌注。将NO电极置于玻璃收集插管内以测量血管流出物中的NO浓度。ANG II以剂量依赖性方式刺激NO释放：0.1 nM、10 nM和1000 nM的ANG II分别使NO氧化电流增加85±18 pA（n = 11）、148±22 pA（n = 11）和193±29 pA（n = 11）。这些电流分别对应于流出物中NO浓度变化3.4±0.5 nM、6.1±1.1 nM和8.2±1.3 nM。LOS（1 μM）和CAN（1 nM）均未显著影响基础NO生成，但两种AT1受体阻滞剂均能显著抑制ANG II（10 nM）诱导的NO释放：LOS（n = 8）抑制77±6%，CAN（n = 8）抑制63±9%。这些结果首次证明ANG II可刺激分离的肾阻力动脉中NO释放，且同时阻断AT1受体会减弱ANG II诱导的NO释放。我们的研究结果表明，肾阻力动脉中ANG II诱导的血管收缩的内皮依赖性调节至少部分是由AT1受体依赖性NO释放介导的。
