Hong Mi Hyeon, Kim Hye Yoom, Jang Youn Jae, Na Se Won, Han Byung Hyuk, Yoon Jung Joo, Seo Chang Seob, Lee Ho Sub, Lee Yun Jung, Kang Dae Gill
Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University, 460 Iksan-daero, Iksan, Jeonbuk 54538, Republic of Korea.
College of Korean Medicine and Professional Graduate School of Korean Medicine, Wonkwang University, 460 Iksan-daero, Iksan, Jeonbuk 54538, Republic of Korea.
Evid Based Complement Alternat Med. 2021 Jul 13;2021:9980429. doi: 10.1155/2021/9980429. eCollection 2021.
In this study, we evaluated the effect of a traditional herbal formula, Ma Huang Tang (MHT), on blood pressure and vasodilation in a rat model of N-nitro-L-arginine methylester- (L-NAME-) induced hypertension. We found that MHT-induced vascular relaxation in a dose-dependent manner in rat aortas pretreated with phenylephrine. However, pretreatment of endothelium-intact aortic rings with L-NAME, an inhibitor of nitric oxide synthesis (NOS), or 1H-[1, 2, 4]-oxadiazole-[4, 3-]-quinoxalin-1-one (ODQ), an inhibitor of soluble guanylyl cyclase, significantly abolished vascular relaxation induced by MHT. MHT also increased the production of guanosine 3',5'-cyclic monophosphate (cGMP) in the aortic rings pretreated with L-NAME or ODQ. To examine the effects of MHT, Sprague Dawley rats were treated with 40 mg/kg/day L-NAME for 3 weeks, followed by administration of 50 or 100 mg/kg/day MHT for 2 weeks. MHT was found to significantly normalize systolic blood pressure and decreased intima-media thickness in aortic sections of rats treated with L-NAME compared to that of rats treated with L-NAME alone. MHT also restored the L-NAME-induced decrease in vasorelaxation response to acetylcholine and endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1) expression. Furthermore, MHT promoted the recovery of renal function, as indicated by osmolality, blood urea nitrogen (BUN) levels, and creatinine clearance. These results suggest that MHT-induced relaxation in the thoracic aorta is associated with activation of the nitric oxide/cGMP pathway. Furthermore, it provides new therapeutic insights into the regulation of blood pressure and renal function in hypertensive patients.
在本研究中,我们评估了传统中药方剂麻黄汤(MHT)对N-硝基-L-精氨酸甲酯(L-NAME)诱导的高血压大鼠模型血压和血管舒张的影响。我们发现,在预先用去氧肾上腺素处理的大鼠主动脉中,MHT以剂量依赖性方式诱导血管舒张。然而,用一氧化氮合成(NOS)抑制剂L-NAME或可溶性鸟苷酸环化酶抑制剂1H-[1,2,4]-恶二唑-[4,3-]-喹喔啉-1-酮(ODQ)对完整内皮的主动脉环进行预处理,可显著消除MHT诱导的血管舒张。MHT还增加了用L-NAME或ODQ预处理的主动脉环中鸟苷3',5'-环磷酸(cGMP)的产生。为了研究MHT的作用,将Sprague Dawley大鼠用40mg/kg/天的L-NAME处理3周,随后给予50或100mg/kg/天的MHT处理2周。与仅用L-NAME处理的大鼠相比,发现MHT可使L-NAME处理的大鼠收缩压显著恢复正常,并减少主动脉切片的内膜中层厚度。MHT还恢复了L-NAME诱导的对乙酰胆碱的血管舒张反应降低以及内皮型一氧化氮合酶(eNOS)和内皮素-1(ET-1)表达。此外,MHT促进了肾功能的恢复,这通过渗透压、血尿素氮(BUN)水平和肌酐清除率来表明。这些结果表明,MHT诱导的胸主动脉舒张与一氧化氮/cGMP途径的激活有关。此外,它为高血压患者血压和肾功能的调节提供了新的治疗见解。