Xavier Fabiano E, Salaices Mercedes, Márquez-Rodas Iván, Alonso María J, Rossoni Luciana V, Vassallo Dalton V, Balfagón Gloria
Departamentos de Fisiología and Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma, C/Arzobispo Morcillo 4, 28029 Madrid, Spain.
J Hypertens. 2004 May;22(5):949-57. doi: 10.1097/00004872-200405000-00017.
We investigated whether chronic ouabain treatment changes the vasoconstrictor responses induced by electrical field stimulation (EFS) in endothelium-denuded rat superior mesenteric arteries and a possible role of neuronal nitric oxide (NO).
Mesenteric arteries from untreated and ouabain-treated rats (approximately equal to 8.0 microg/kg per day, for 5 weeks) were used in this study. Vascular reactivity was analyzed by isometric tension recording. Expression of the neuronal NO synthase isoform was analyzed by Western blot. Noradrenaline release was evaluated in segments incubated with [H]noradrenaline.
Systolic (SBP) and diastolic (DBP) blood pressure were higher in ouabain-treated rats than in untreated rats (SBP, untreated: 120 +/- 3.5 mmHg versus ouabain-treated: 150 +/- 4.7 mmHg, P < 0.01; DBP, untreated: 87 +/- 3.0 mmHg versus ouabain-treated: 114 +/- 2.6 mmHg, P < 0.001). EFS-induced vasoconstrictions were smaller in arteries from ouabain-treated rats than in those from untreated animals, while the EFS-induced [H]noradrenaline release and the vasoconstriction induced by exogenous noradrenaline (1 nmol/l-10 micromol/l) remained unmodified. The non-selective NO synthase (NOS) inhibitor, N-nitro-L-arginine methyl ester (100 micromol/l), increased the EFS-induced vasoconstriction in mesenteric arteries from both groups, although the effect was more pronounced in segments from ouabain-treated rats. The selective neuronal NOS inhibitor, 7-nitroindazole (7-NI; 100 micromol/l) increased EFS-induced contraction only in segments from ouabain-treated rats. Neuronal NOS expression was greater in the mesenteric arteries from ouabain-treated rats than in those from untreated animals. Sodium nitroprusside (0.1 nmol/l-10 micromol/l) induced a similar vasodilatation in segments from both groups.
These results suggest that chronic ouabain treatment is accompanied by an increase in neuronal NO release that reduces EFS-induced vasoconstriction.
我们研究了慢性哇巴因治疗是否会改变去内皮大鼠肠系膜上动脉中电场刺激（EFS）诱导的血管收缩反应以及神经元型一氧化氮（NO）的可能作用。
本研究使用了未处理和经哇巴因处理的大鼠（约8.0微克/千克/天，持续5周）的肠系膜动脉。通过等长张力记录分析血管反应性。通过蛋白质免疫印迹分析神经元型一氧化氮合酶同工型的表达。在与[H]去甲肾上腺素孵育的节段中评估去甲肾上腺素的释放。
经哇巴因处理的大鼠的收缩压（SBP）和舒张压（DBP）高于未处理的大鼠（SBP，未处理：120±3.5毫米汞柱，经哇巴因处理：150±4.7毫米汞柱，P<0.01；DBP，未处理：87±3.0毫米汞柱，经哇巴因处理：114±2.6毫米汞柱，P<0.001）。经哇巴因处理的大鼠的动脉中EFS诱导的血管收缩比未处理动物的动脉中的小，而EFS诱导的[H]去甲肾上腺素释放和外源性去甲肾上腺素（1纳摩尔/升 - 10微摩尔/升）诱导的血管收缩保持不变。非选择性一氧化氮合酶（NOS）抑制剂N-硝基-L-精氨酸甲酯（100微摩尔/升）增加了两组肠系膜动脉中EFS诱导的血管收缩，尽管在经哇巴因处理的大鼠的节段中作用更明显。选择性神经元型NOS抑制剂7-硝基吲唑（7-NI；100微摩尔/升）仅在经哇巴因处理的大鼠的节段中增加了EFS诱导的收缩。经哇巴因处理的大鼠的肠系膜动脉中的神经元型NOS表达高于未处理动物的。硝普钠（0.1纳摩尔/升 - 10微摩尔/升）在两组的节段中诱导了相似的血管舒张。
这些结果表明，慢性哇巴因治疗伴随着神经元型NO释放增加，从而减少了EFS诱导的血管收缩。
