The present study was performed to examine the antihypertensive effect of neferine in hypertensive rats and its relaxant mechanisms in isolated rat thoracic aorta. The antihypertensive effect was evaluated by tail-cuff methods on NG-nitro-L-arginine methyl ester (L-NAME) (40 mg/kg BW) 4-week hypertensive-induced hypertensive rats. The vasorelaxant effect and its mechanisms were studied by the organ bath technique in the thoracic aorta isolated from normotensive rats. The results indicated that the treatment of neferine (1 mg/kg and 10 mg/kg) markedly decreased the systolic blood pressure (SBP) when compared with the hypertension group (137.75 ± 10.14 mmHg and 132.23 ± 9.5 mmHg, respectively, p < 0.001), without affecting the heart rate. Moreover, neferine (10-12 - 10-4 M) exhibited concentration-dependent vasorelaxation in endothelium-intact rings (Emax values = 98.95 ± 0.66% and pD2 = 7.93 ± 0.28) and endothelium-denuded rings (Emax values = 90.61 ± 1.91% and pD2 = 6.85 ± 0.36). The effects of neferine were reduced by pre-incubation with L-NAME and 1H-[1,2,4]oxadiazolo[4,3-a] quinoxalin-1-one (ODQ) but not with pre-incubation with indomethacin and K+channel blockers. Neferine attenuated the contractions induced by phenylephrine and caffeine in a Ca2+-free solution and also inhibited in CaCl2- and phenylephrine-induced contracted rings. Our study suggests that neferine exhibited hypertensive potential, induced vasorelaxation through the endothelium nitric oxide synthase (eNOS)/nitric oxide (NO)/soluble guanylyl cyclase (sGC) pathway and involved the modulation of Ca2+ influx through Ca2+ channels and intracellular Ca2+ release from the sarcoplasmic reticulum.

中文翻译：

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Neferine 对大鼠的血管舒张和抗高血压作用：一项体外和体内研究

本研究旨在检查奈弗林对高血压大鼠的抗高血压作用及其在离体大鼠胸主动脉中的松弛机制。通过尾套法对 NG-硝基-L-精氨酸甲酯 (L-NAME) (40 mg/kg BW) 4 周高血压诱导的高血压大鼠的抗高血压作用进行评估。血管舒张作用及其机制通过器官浴技术在从正常血压大鼠中分离出来的胸主动脉中进行研究。结果表明，与高血压组（分别为 137.75 ± 10.14 mmHg 和 132.23 ± 9.5 mmHg，p < 0.001）相比，neferine（1 mg/kg 和 10 mg/kg）的治疗显着降低了收缩压（SBP） )，而不会影响心率。而且，neferine (10-12 - 10-4 M) 在内皮完整环（Emax 值 = 98.95 ± 0.66% 和 pD2 = 7.93 ± 0.28）和内皮裸露环（Emax 值 = 90.61 ± 1.91%）中表现出浓度依赖性血管舒张pD2 = 6.85 ± 0.36）。通过与 L-NAME 和 1H-[1,2,4]oxadiazolo[4,3-a] quinoxalin-1-one (ODQ) 预孵育可降低 neferine 的作用，但与吲哚美辛和 K 预孵育不会降低+通道拦截器。Neferine 减弱了无 Ca2+ 溶液中苯肾上腺素和咖啡因引起的收缩，并且还抑制了 CaCl2-和去氧肾上腺素引起的收缩环。我们的研究表明，neferine 具有高血压潜力，