去甲乌药碱对正常血压大鼠心血管系统的影响。
Cardiovascular effects induced by reticuline in normotensive rats.
作者信息
Dias Katy Lísias, Da Silva Dias Celidarque, Barbosa-Filho José Maria, Almeida Reinaldo Nóbrega, De Azevedo Correia Nadja, Medeiros Isac Almeida
机构信息
Laboratório de Tecnologia Farmacêutica, Universidade Federal da Paraíba, João Pessoa-PB, Brazil.
出版信息
Planta Med. 2004 Apr;70(4):328-33. doi: 10.1055/s-2004-818944.
The cardiovascular effects of reticuline, isolated in a pure form from the stem of Ocotea duckei Vattimo, were studied in rats by using a combined in vivo and in vitro approach. In normotensive rats, reticuline (5, 10 and 20 mg/kg, i. v., randomly) injections produced an intense hypotension. This hypotensive response was attenuated after either, L-NAME (20 mg/kg, i. v.), a nitric oxide (NO) synthase inhibitor, or atropine (2 mg/kg, i. v.), a muscarinic receptor antagonist. In isolated rat aortic rings with intact endothelium, reticuline (3 x 10 ( - 6), 3 x 10 ( - 5), 3 x 10 ( - 4), 9 x 10 ( - 4) and 1.5 x 10 ( - 3) M) inhibited in a concentration-dependent manner the contractions induced by phenylephrine (1 microM), KCl (80 mM) and KCl (30 mM), [IC (50) = (0.4 +/- 0.1, 2.4 +/- 0.4 and 3 +/- 0.4) x 10 ( - 4) M, respectively). The effect of reticuline on phenylephrine-induced contractions was attenuated by removal of the vascular endothelium [IC (50) = (2.5 +/- 0.7) x 10 ( - 4) M]. Similar results were obtained after pretreatment of the rings with L-NAME 100 microM [IC (50) = (1.3 +/- 0.1) x 10 ( - 4) M], L-NAME 300 microM [IC (50) = (3 +/- 0.3) x 10 ( - 4) M] or atropine 1 microM [IC (50) = (1.2 +/- 0.2) x 10 ( - 4) M]. On the other hand, the effect of reticuline on phenylephrine-induced contractions was not affected by indomethacin 1 microM [IC (50) = (0.7 +/- 0.3) x 10 ( - 4) M]. Reticuline (3 x 10 ( - 6), 3 x 10 ( - 5), 3 x 10 ( - 4), 9 x 10 ( - 4) and 1.5 x 10 ( - 3) M) antagonized CaCl (2)-induced contractions, and also inhibited the intracellular calcium dependent transient contractions induced by norepinephrine (1 microM), but not those induced by caffeine (20 mM). These results suggest that the hypotensive effect of reticuline is probably due to a peripheral vasodilation in consequence of: 1) muscarinic stimulation and NOS activation in the vascular endothelium, 2) voltage-dependent Ca (2+) channel blockade and/or 3) inhibition of Ca (2+) release from norepinephrine-sensitive intracellular stores.
采用体内和体外相结合的方法，在大鼠中研究了从奥氏厚壳桂（Ocotea duckei Vattimo）茎中分离得到的纯品网叶番荔枝碱的心血管效应。在正常血压大鼠中，静脉随机注射网叶番荔枝碱（5、10和20mg/kg）会引起强烈的低血压。一氧化氮（NO）合酶抑制剂L-NAME（20mg/kg，静脉注射）或毒蕈碱受体拮抗剂阿托品（2mg/kg，静脉注射）给药后，这种降压反应减弱。在具有完整内皮的离体大鼠主动脉环中，网叶番荔枝碱（3×10⁻⁶、3×10⁻⁵、3×10⁻⁴、9×10⁻⁴和1.5×10⁻³M）以浓度依赖性方式抑制去氧肾上腺素（1μM）、氯化钾（80mM）和氯化钾（30mM）诱导的收缩[IC₅₀分别为(0.4±0.1、2.4±0.4和3±0.4)×10⁻⁴M]。去除血管内皮后，网叶番荔枝碱对去氧肾上腺素诱导收缩的作用减弱[IC₅₀=(2.5±0.7)×10⁻⁴M]。用100μM的L-NAME[IC₅₀=(1.3±0.1)×10⁻⁴M]、300μM的L-NAME[IC₅₀=(3±0.3)×10⁻⁴M]或1μM的阿托品[IC₅₀=(1.2±0.2)×10⁻⁴M]预处理环后，得到了类似的结果。另一方面，1μM的吲哚美辛[IC₅₀=(0.7±0.3)×10⁻⁴M]对网叶番荔枝碱对去氧肾上腺素诱导收缩的作用没有影响。网叶番荔枝碱（3×10⁻⁶、3×10⁻⁵、3×10⁻⁴、9×10⁻⁴和1.5×10⁻³M）拮抗氯化钙诱导的收缩，也抑制去甲肾上腺素（1μM）诱导的细胞内钙依赖性瞬时收缩，但不抑制咖啡因（20mM）诱导的收缩。这些结果表明，网叶番荔枝碱的降压作用可能归因于外周血管舒张，其原因如下：1）血管内皮中的毒蕈碱刺激和NOS激活；2）电压依赖性钙通道阻滞和/或3）抑制去甲肾上腺素敏感的细胞内钙库释放钙。
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