Patzak Andreas, Mrowka Ralf, Storch Eberhard, Hocher Berthold, Persson Pontus B
Johannes-Müller-Institute of Physiology, Humboldt-University of Berlin, Berlin, Germany.
Department of Nephrology, University-Hospital Charité, Humboldt-University of Berlin, Berlin, Germany.
J Am Soc Nephrol. 2001 Jun;12(6):1122-1127. doi: 10.1681/ASN.V1261122.
The present study was performed to evaluate angiotensin II (Ang II)-nitric oxide (NO) interaction in afferent arterioles (Af) of wild-type mice and mice that are homozygous (-/-) for disruption of the endothelial NO synthase (eNOS) gene. Af were microperfused, and the dose responses were assessed for the NO precursor L-arginine (n = 4), NO inhibitor NG-nitro-L-arginine methyl ester (L-NAME, n = 5), L-NAME after pretreatment with L-arginine (n = 5), Ang II (n = 8), and Ang II after pretreatment with L-NAME (n = 7). Acute administration of L-arginine and L-NAME (both in doses from 10(-6) to 10(-3) mol/L) did not change arteriolar diameter. Moreover, pretreatment with L-arginine did not change the response to L-NAME. However, Ang II, applied in doses of 10(-12), 10(-10), 10(-8), and 10(-6) mol/L, significantly reduced the lumen to 66.5 +/- 7.0% and 62.2 +/- 8.0% at 10(-8) and 10(-6) mol/L Ang II, respectively. The contraction was augmented after L-NAME pretreatment (19.5 +/- 13.6% and 25.5 +/- 10.2% at 10(-8) and 10(-6) mol/L Ang II, respectively). In eNOS (-/-) mice (n = 8), the response to Ang II also was enhanced (9.1 +/- 6.0% and 11.2 +/- 8.2% at 10(-8) and 10(-6) mol/L Ang II, respectively). Female mice did not differ from male mice in their reactivity to Ang II (n = 9) and Ang II + L-NAME pretreatment (n = 11). The study shows that (1) it is feasible to microperfuse mouse Af, (2) the basal production of endothelial NO is very low and not inducible by L-arginine in Af of mice, and (3) a counteracting effect of NO is initiated by Ang II. High Ang II sensitivity in eNOS (-/-) mice underscores the considerable role of endothelial-derived NO to balance Ang II vasoconstriction in Af.
本研究旨在评估野生型小鼠和内皮型一氧化氮合酶（eNOS）基因敲除纯合子（-/-）小鼠的传入小动脉（Af）中血管紧张素II（Ang II）与一氧化氮（NO）的相互作用。对Af进行微量灌注，并评估一氧化氮前体L-精氨酸（n = 4）、一氧化氮抑制剂NG-硝基-L-精氨酸甲酯（L-NAME，n = 5）、L-精氨酸预处理后的L-NAME（n = 5）、Ang II（n = 8）以及L-NAME预处理后的Ang II（n = 7）的剂量反应。急性给予L-精氨酸和L-NAME（剂量均为10(-6)至10(-3) mol/L）均未改变小动脉直径。此外，L-精氨酸预处理并未改变对L-NAME的反应。然而，以10(-12)、10(-10)、10(-8)和10(-6) mol/L的剂量应用Ang II时，在10(-8)和10(-6) mol/L Ang II时，管腔分别显著缩小至66.5±7.0%和62.2±8.0%。L-NAME预处理后收缩增强（在10(-8)和10(-6) mol/L Ang II时分别为19.5±13.6%和25.5±10.2%）。在eNOS（-/-）小鼠（n = 8）中，对Ang II的反应也增强（在10(-8)和10(-6) mol/L Ang II时分别为9.1±6.0%和11.2±8.2%）。雌性小鼠在对Ang II（n = 9）和Ang II + L-NAME预处理（n = 11）的反应性方面与雄性小鼠无差异。该研究表明：（1）对小鼠Af进行微量灌注是可行的；（2）内皮型一氧化氮的基础生成量非常低，且在小鼠的Af中不能被L-精氨酸诱导；（3）Ang II引发了一氧化氮的拮抗作用。eNOS（-/-）小鼠中对Ang II的高敏感性强调了内皮源性一氧化氮在平衡Af中Ang II血管收缩方面的重要作用。
