Thorup C, Kornfeld M, Goligorsky M S, Moore L C
Department of Physiology, Göteborg University, Sweden.
J Am Soc Nephrol. 1999 Jan;10 Suppl 11:S220-4.
Nitric oxide (NO) is known to modulate the vascular effects of angiotensin II (AngII) in the kidney. To investigate the effect of AngII on NO release, a new technique was used that employs an NO-sensitive microelectrode to measure NO release from the vascular endothelium of perfused renal resistance arteries (tertiary branches of the renal artery or primary arcuate arteries) in vitro. The vessels were microdissected from isolated perfused rat kidneys, cannulated, and perfused at constant flow and pressure with Krebs-Ringer bicarbonate solution. The electrode was placed inside the glass collection cannula to measure vessel effluent NO concentration. Addition of AngII to the perfusate stimulated NO release in a dose-dependent manner; 0.1, 10, and 1000 nM AngII 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, 6.1+/-1.1, and 8.2+/-1.3 nM, respectively. The presence of 0.1 mM N(G)-nitro-L-arginine methyl ester in the perfusate significantly reduced the response to 10 nM AngII by 90.5+/-3.4% (n=5). Neither losartan (1 microM) nor candesartan (1 nM) significantly affected basal NO production, but both of these AT1-receptor blockers markedly blunted NO release in response to AngII (10 nM): 77+/-6% inhibition with losartan (n=8) and 63+/-9% with candesartan (n=8). These results demonstrate that AngII stimulates N(G)-nitro-L-arginine methyl ester-inhibitable NO release in isolated renal resistance arteries. Because the response was significantly blunted by AT1 receptor blockade, the findings suggest that endothelium-dependent modulation of AngII-induced vasoconstriction in renal resistance arteries is mediated, at least in part, by AT1 receptor-dependent NO release.
已知一氧化氮（NO）可调节肾脏中血管紧张素II（AngII）的血管效应。为了研究AngII对NO释放的影响，采用了一种新技术，该技术使用对NO敏感的微电极在体外测量灌注的肾阻力动脉（肾动脉的三级分支或初级弓形动脉）血管内皮释放的NO。血管从分离的灌注大鼠肾脏中显微解剖出来，插管，并以恒定流量和压力用 Krebs-Ringer 碳酸氢盐溶液灌注。将电极置于玻璃收集插管内以测量血管流出液中的NO浓度。向灌注液中添加AngII以剂量依赖性方式刺激NO释放；0.1、10和1000 nM的AngII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液中NO浓度变化3.4±0.5、6.1±1.1和8.2±1.3 nM。灌注液中存在0.1 mM的N(G)-硝基-L-精氨酸甲酯可使对10 nM AngII的反应显著降低90.5±3.4%（n = 5）。氯沙坦（1 μM）和坎地沙坦（1 nM）均未显著影响基础NO生成，但这两种AT1受体阻滞剂均显著减弱了对AngII（10 nM）的NO释放反应：氯沙坦抑制77±6%（n = 8），坎地沙坦抑制63±9%（n = 8）。这些结果表明，AngII刺激分离的肾阻力动脉中N(G)-硝基-L-精氨酸甲酯可抑制的NO释放。由于AT1受体阻断使反应显著减弱，这些发现表明，肾阻力动脉中AngII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。
