Carvedilol action is dependent on endogenous production of nitric oxide
Carvedilol action is dependent on endogenous production of nitric oxide
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DOI：
10.1016/j.amjhyper.2005.11.011
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发表时间：
2006-04-01
影响因子：
3.2
通讯作者：
Carmo, MM
中科院分区：
文献类型：
--
作者：
Afonso, RA;Patarrao, RS;Carmo, MM
背景：卡维地洛是一种肾上腺素受体阻滞剂和自由基清除剂，用于治疗高血压和心力衰竭。然而，这些机制不能完全解释其治疗作用。在这些研究中，我们测试的假设，卡维地洛的行动是与合成/释放一氧化氮（NO）。方法：雄性Wistar大鼠（n = 22），9周龄，麻醉与戊巴比妥钠腹腔注射。在整个实验过程中监测平均动脉压和动脉NO水平。Carvedilol在NO合酶（NOS）抑制剂N-ω-硝基-精氨酸甲酯（N-omega-nitro-Larginine methyl ester）给药之前和之后，（L-NAME，5mg/kg，iv）。卡维地洛可显著降低基础动脉压（从126.6 +/- 4.3 mm Hg到75.9 +/- 3.0 mm Hg，P < .001）和NO水平显著增加（从17.9 +/- 1.7 μ mol/L到32.2 +/- 2.5 μ mol/L，P < .001）。给予L-NAME后，动脉压升高（129.9 +/- 5.0 mm Hg，P <0.001），同时NO水平降低（13.4 +/- 1.6 μ mol/L，P <0.01）。第二次卡维地洛给药（后L-NAME）不影响动脉压（108.3 +/- 8.0 mm Hg）或NO水平（22.1 +/- 1.3 μ mol/L）。结论：我们的研究结果表明，卡维地洛诱导的血压降低与血浆NO水平的增加有关。此外，NOS抑制导致卡维地洛血流动力学效应和血浆NO水平受损。因此，这些结果与卡维地洛的血流动力学效应部分依赖于内源性NO产生的假设一致。(c)2006年美国高血压杂志有限公司
Background: Carvedilol is known to be an adrenoreceptor blocker and free radical scavenger, used in hypertension and cardiac failure. However, its therapeutic actions cannot be fully explained by these mechanisms. In these studies, we tested the hypothesis that carvedilol action is associated with the synthesis/release of nitric oxide (NO).Methods: Male Wistar rats (n = 22), 9 weeks old, were anesthetized with an intraperitoneal injection of sodium pentobarbital. Mean arterial pressure and arterial NO levels were monitored throughout the experiments. Carvedilol (1 mg/kg, intravenously [iv]) effects were evaluated before and after NO synthase (NOS) inhibitor N-omega-nitro-Larginine methyl ester (L-NAME, 5 mg/kg, iv).Results: Carvedilol induced a significant decrease in basal arterial pressure (from 126.6 +/- 4.3 mm Hg to 75.9 +/- 3.0 mm Hg, P < .001) and significant increase in NO levels (from 17.9 +/- 1.7 mu mol/L to 32.2 +/- 2.5 mu mol/L, P < .001). After administration of L-NAME the arterial pressure increased (129.9 +/- 5.0 mm Hg, P < .001) with concomitant decrease in NO levels (13.4 +/- 1.6 mu mol/L, P < .01). The second carvedilol administration (post-L-NAME) did not affect either arterial pressure (108.3 +/- 8.0 mm Hg) or NO levels (22.1 +/- 1.3 mu mol/L).Conclusions: Our results suggest that the carvedilol-induced decrease of blood pressure is associated with an increase of plasma NO levels. Furthermore, NOS inhibition results in impairment of carvedilol hemodynamic effects and plasma NO levels. Therefore, these results are consistent with the hypothesis that the hemodynamic effect of carvedilol is in part dependent on endogenous NO production. (c) 2006 American Journal of Hypertension, Ltd.