Studies Of Hypotensive Effects Of Persimmon Leaf Flavonoids On L-NAME Induced Hypertensive In Rats And Its Related Mechanisms

OBJECTIVE:To study hypotensive effects of persimmon leaf flavonoids (PLF)on L-NAME(N^G-nitro-L-arginine-methylester)induced hypertensive in rats and its related mechanisms.METHODS:Hypertensive rats were produced by L-NAME.(1)Multimedia biological signal analysis system was used to record systolic blood pressure(SP),diastolic blood pressure(DP)and heart rate (HR)by carotid artery intubation before and after PLF was administrated via femoral vein.(2)PLF was given intragastrically for 8 weeks,and blood pressure and HR were measured weekly with tail-cuff method before and after the administration of medicine.(3)Cardiac cannula and MS4000 multimedia biological signal analysis system were used for the examination of the hemodynamics index:ventricle systolic pressure(LVSP),left ventricle ending diastolic pressure(LVEDP),heart rate(HR),left ventricle pressure maximum rising rate of speed(dp/dtmax),left ventricle pressure maximum descent rate of speed(-dp/dtmax),and t-dp/dtmax in rats before and after administration of PLF. (4)Langendorff-perfusion isolated rat hearts were prepared and the effect of PLF on myocardial contractility was observed by MS 4000 bio-signal analytical system.(5)The experimental method of smooth muscle in vitro was used to observe the effect of PLF on contraction of aortic strips induced by KCl,NE and CaCl₂.(6)At the end of the 8th week,the rats were killed,then their hearts were quickly removed,then the left ventricle was weighed,the left ventricular mass index(LVMI)was calculated and the left ventricular thickness was measured. Pathomorphological changes of the left ventricle were observed through hematoxylin-eosin staining,and the transverse diameters of myocardium(TDM) were measured.(7)At the end of the 8th week,the rats were killed.The plasma concentrationsof angiotensinâ…¡(Angâ…¡)and endothelin(ET)were measured by radioimm-unoassav and the serum concerntration of nitric oxide(NO)was tested by nitric acid deoxidized enzyme.RESULTS:(1)In acute hypotensive experiments,PLF could markedly reduce the BP in normal rats and L-NAME induced hypertensive in rats(P＜0.05 or P＜0.01),but did not influence the effects of norepinephrine(NE)and isoprenaline(ISO).(2)After intragastric administration of PLF for 8 weeks,BP(P＜0.05 or P＜0.01)was significantly reduced with a dose-dependent manner.In PLF_H group,an obvious reduction of BP(P＜0.05)occured in 2^thweek after administration and reached peak effect in the 4^thweek.In PLF_L and PLF_M groups,an obvious reduction of the BP(P＜0.05) was found in the 3^thweek and reached peak effect in the 4^thweek.One week after the withdrawal of drugs,BP returned to the level before treatment in Ver group but it took two weeks to in PLF groups.(3)PLF could significantly decrease LVSP,dp/dtmax and HR(P＜0.05 or P＜0.01),but did not have obvious influence in LVEDP and-dp/dtmax.(4)PLF could significantly decrease myocardial contractility(P＜0.05 or P＜0.01).(5)PLF could inhibit the contraction of aortic strips induced by KCl,NE and CaCl₂,so that KCl,NE and CaCl₂ concentration response curves were shifted rightward,which were similar to verapamil(Ver).The effect may be due to the inhibition of the calcium channel of aortic smooth muscle.PLF showed major effect on potential dependent Ca²⁺ channel(PDC).(6)LVMI in PLF_H group was decreased compared with L-NAME group(P＜0.05).Left ventricular thickness and TDM in PLF_L group and PLF_M group were also decreased compared with L-NAME group(P＜0.05 or P＜0.01).(7)After 8 weeks of oral administration,compared with L-NAME group,PLF groups elevated serum NO concentrations(P＜0.05 or P＜0.01)and lowered plasma concentrations of Angâ…¡and ET(P＜0.05 or P＜0.01).CONCLUSION:(1)PLF could decrease BP and HR in normal rats and L-NAME induced hypertensive in rats.(2)PLF could relieve left ventricular hypertrophy in L-NAME induced hypertensive in rats.(3)The hypotensive effects of PLF on L-NAME induced hypertensive in rats were not related to blocking a receptor orβreceptor.Its antihypertention mechanism may be due to its negative inotropic action and negative chronotropic effect by selectively blocking potential dependent calcium channel,and its adjustion of the imbalance of cardiovascular active substances by increasing the release of endogenous vasodilators and reducing the release of endogenous vasoconstrictors.