| ObjectiveSince Uncaria rhynchophylla and Gastrodia elata, Chinese traditional medicininal herbs used for antihypertension, usually should be prescribed together, the present research was designed to investigate the effects of Rhynchophylla total alkaloids(RTA) and gastrodin, active ingredients out of Uncaria rhynchophylla and Gastrodia elata, on blood pressure variability, heart rates variability and baroerflex sensitivity, and to clarify whether they have protective effects on hypertensive target organs. It was also investigated whether the combination administration of RTA and gastrodin would have synergistic effects on antihypertension.MethodBlood pressure monitoring system for conscious freely moving rats was employed to get aparameters such as blood pressure, heart rates and their variability and baroerflex sensitivity being administrated RTA (25, 50, 100, 200mg/kg), gastrodin (8, 80, 800mg/kg) respectively in all 45 spontaneous hypertensive rats(SHR), which were divided into 11 groups randomly according to administration dosages. The mixture of these two agents (50+8, 50+80, 50+800mg/kg) was also used to get synergistic effects on antihypertension, and probability sum test (q-test) was used to determine synergistic aparameters.In order to investigate the effects on hypertensive target organs, histopathological examinations were performed on brains, hearts, kidneys and livers in 30 SHRs administrated by RTA (50mg/kg/day), RTA and gastrodin(50+62.5mg/kg/day) for 20 weeks with Tianmagouteng Granules (2.5g/kg/day) as positive controls.ResultsBlood pressure and the heart rates decreased significantly more than 15mmHg and 1.5hrs after RTA administrated i.p. in SHRs, and the effective dosage of RTA antihypertension was about 50~200mg/kg according to the dose-effect relationship. However, blood pressure variability (BPV) or baroreflex sensitivity (BRS) had no signicant change due to RTA administrated i.p. in SHRs. On the other hand, blood pressure, heart rates and their variability remained no change in SHRs, even if the dosage of gastrodin i.p. could be more than 800mg/kg, which was quite different from common knowledge. But BRS was improved significantly in SHRs after gastrodin administrated i.p. in the range of 8~800mg/kg.As for the combination usage of RTA and gastrodin, antihypertensive effect and improvement of BRS were obtained in the dosage of 50+8, 50+80, 50+800mg/kg. According to the result of q-test, it was suggested that synergetic effects of antihypertension and BRS enhancement between RTA and gastrodin be positive. Although neither RTA nor GAS changed BPV, BPV decreased significantly due to combination using of RTA and gastrodin in the dosage of 50+800mg/kg.Histopathological examinations revealed the changes of target organs after RTA and gastrodin administrated for 20 weeks in SHRs. Besides similar inflammation damage, there were no significant changes in brain, heart or kidney tissues slices under microscopes. Those specific damages of hypertension, such as heart congestion, kidney anlosis, or brain infarction were not been observed. But significant liver damage, including inflammation, necrosis and fibroplasias was observed in liver slices from SHRs after administrated by RTA.ConculusionRTA was effective in antihypertension and decreasing heart rate in SHRs with a dose-effect manner, but has no effect on BPV or BRS. Blood pressure did not be changed by gastrodin i.p., but baroreflexsensitivity improved in SHRs due to gastrodin administration. The combination administration of RTA and gastrodin had synergistic effects on antihypertension, and BRS improved as well.RTA and combination administration of RTA and gastrodin could protect SHRs from target organs damages, but hepatoxicity of RTA induced liver damages in the rats. |
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