With Dogwood Decoction On Blood Pressure And Cardiac Function In Spontaneously Hypertensive Rats And Mechanism Research

Background: Hypertension (high blood pressure) as a kind of chronic disease mainly manifests as elevated systemic circulation arterial pressure, with higher prevalence in our country, but the receiving treatment rate, aware rate and control rate remains unsatisfactory. Hypertension can trigger many disease as a risk factor, it leads to not only abnormality of hemodynamics, but also damages targeted organ like heart, brain, kidney, etc. Treatment of hypertension aims to control blood pressure, most important is to prevent and lower the incidence of cerebrovascular diseases or complications caused by high blood pressure and decrease the mortality of patients in urgency or emergency. This opinion accords with the basic theory of holistic concept and treatment by syndrome differentiation of Traditional Chinese Medicine(TCM).It is significant to dig out herbal pair or herbal complex with good therapeutic effect in lowering blood pressure, regulating metabolism, protecting and inversing the damages of targeted organs by combing syndrome differentiation with pattern differentiation.Results from pharmacological studies indicate that Rhizoma coptidi and its main component can decrease the blood pressure by competitively interrupting a receptor function of vascular smooth muscle, activating M receptor, inhibiting activity of cholinesterase, inhibiting norepinephrine release, releasing NO, activating K⁺ channel and inhibiting the intracellular release of Ca²⁺. Evodia rutaecarpa (Joss.) Benth and its main component has the function of lowering blood pressure by activatingβreceptor, promoting synthesis of prostaglandin and histamine, and extending the peripheral vessel. According to TCM basic theory, flairing up of liver-fire plays an important role in the pathogenesis of hypertension. Liver-fire invades the stomach, which results in the disharmony of liver and stomach, and heat stagnation in the two viscera. So the disease manifests as the symptoms like headache, dizziness, hiccup, etc. Rhizoma coptidi and Evodia rutaecarpa (Joss.) Benth both can relieve stagnation by dispelling liver-fire. It deserves us making researches at this aspect to explore the possible acting mechanism. Objetives: This research is designed to clarify the function of combined useRhizoma coptidi and Evodia rutaecarpa (Joss.) Benth in spontaneously hypertensiverat(SHR); To find out the most optimal dosage of combined use, Meanwhile furtherstudy of the compatibility of the two drugs in heart function; To detect the volumeendothelin(ET),calcitonin gene-related peptide (CGRP) , angiotensin and aldosteroneof RAAS system of SHR plasma in combined group; To explore related mechanismand relation of blood pressure decreasing with ET and CGRP; To explore whetherthese two herbs can lower blood pressure by improving RAAS, regulatingneuropeptide level; To provide scientific evidence for herbal pair of Rhizoma coptidiand Evodia rutaecarpa (Joss.) Benth in the treatment of hypertension and improvingthe function of the heart ; To rich basic and clinical research of TCM in the treatmentof EH; To add an economic and effective complex medicine for EH treatment in TCM.Methods: In this experiment, and 13-week-old SHR rats and Wistar Kyoto rat(WKY)for the study, will speak in Wuzhuyu according 6:1,3:1,1:1,1:3,1:6．The six werecomposed of different groups LY1, LY2, LY3, LY4,LY5,the five dose groups, 56 SHRwill be divided into model (Model),nifedipine (Nif),LY1 group,LY2 group, LY3group,LY4 group and LY5 group, eight normal WKY rats to normal control group (WKY),a total of eight groups, each of the four male and female. WKY group and Model groupby 10ml/kg·d;The dosage gives the physiological saline, the Nif group by 1mg/kg·d;Thedosage gives the niter benzene horizontal solution, the Chinese medicine group by10ml/kg·d; The dosage gives to blend the dosage correspondingly the thick decoctum,fills the stomach 4 weeks continuously, all medicine was given by adding pressure fromtail, the survey wil be done in front of filling the stomach and after filling the stomach atthe first day 2h,4 h,6h,8h different time compartment and the first week to the forth weeksoberly time tail artery systolic pressure.4th weekend in rats under anesthesia will be donecardiac catheterization to measure heart rate and hemodynamic parameters of leftventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP),maximal left ventricular pressure rise (+dp/dtmax), maximal left ventricular pressure risefall (-dp/atmax), and ET, CGRP, AngⅡ, ALD content in plasma from rat aortic blood,thefinal results from statistical will be analyzed by spss13．0 software. Result:(1) Rhizoma coptidi, Evodia rutaecarpa (Joss.) Benth compatibility of different doses of blood pressure in SHR : WKY group, 13 weeks of gavage in SHR, significantly higher blood pressure levels, averaging 203mmHg.There was significant difference (P<0．01) . Model rats at the time of blood pressure with age as a consistent upward growth in the fourth week of the highest levels of blood pressure, There was significant difference (P<0．01) . And the Model group, the rats around Nif blood pressure was significantly decreased (P<0．01) gavage medicine five rats around the level of blood pressure in both numerical largely on the fall in which LY2．LY3 rats around blood pressure was significantly decreased (P<0．01) , Rhizoma coptidi, Evodia rutaecarpa (Joss.) Benth to 3:1 and 1:1 Compatibility at a dose of antihypertensive effect of the most obvious, Nif blood pressure in rats showed no difference (P>0．05) .(2) Rhizoma coptidi, Evodia rutaecarpa (Joss.) Benth 3:1 Dosage of blood pressure in SHR immediate impact : Model group, 3:1 Compatibility of a dose in rats , in 2hours, 4hours lower blood pressure have very significant differences (P<0．01) , and in 6 hours, 8 hours lowering blood pressure was also a significant difference (P<0．05) .(3) Rhizoma coptidi, Evodia rutaecarpa (Joss.) Benth 3:1 Dosage right SHR hemodynamic effects : Model rats heart rate significantly accelerate WKY group, and 3:1 dose combinations rats WKY heart rate compared with no significant difference (P> 0．05) . Model rat carotid artery of the heart rate to accelerate and hemodynamic parameters LVEDP, LVSP, w ere reduced to that of normal rats WKY group, There was very significant difference (P<0．01) and Nif Group, 3:1 dose combinations rats compared with normal rat carotid artery pressure increased value, reduced hemodynamic parameters; Model and more rats, and Nif Group, 3:1 dose combinations in the hemodynamic parameters LVEDP, LVSP,±dp/dtmax have improved, statistically significant or very significant difference (P<0．05 or P<0．01) .(4) Rhizoma coptidi, Evodia rutaecarpa (Joss.) Benth 3:1 Dosage right SHR plasma ET, CGRP, AngⅡ, the content of ALD; and the Model rats, the Nif group and 3:1 dose combinations rat plasma ET, ALD content, a significant difference (P<0．05) , while the three : a dose combinations can be significantly increased in rats CGRP content than Nif rats obviously(P<0．01) , Meanwhile two rats AngⅡcontent compared with normal rats no significant difference (P>0．05) . Conclusion:1．Rhizoma coptidi, Evodia rutaecarpa (Joss.) Benth different doses varying degrees compatibility can reduce blood pressure in SHR, Rhizoma coptidi,Evodia rutaecarpa (Joss.) Benth 3:1 and 1:1 Dosage antihypertensive effect when the most obvious.2．Rhizoma coptidi, Evodia rutaecarpa (Joss.) Benth to 3:1 Dosage could significantly lower SHR plasma endothelin, angiotensinⅡ, aldosterone levels, and elevated calcitonin gene-related peptide.3．Rhizoma coptidi, Evodia rutaecarpa (Joss.) Benth to 3:1 Dosage could significantly slow down the heart rate SHR, SHR improve heart function.4．Rhizoma coptidi, Evodia rutaecarpa (Joss.) Benth to 3:1 Dosage could significantly lower blood pressure in SHR. improve cardiac function and its mechanism may reduce plasma endothelin, angiotensinⅡ, aldosterone content increased calcitonin gene-related peptide content.