Effect Of Ethanol Extract Of Rubus Chingii Hu On The Vasodilation Function And Hemodynamics

ObjectiveRaspberry is the dried fruit of Rosaceae Rubus chingii Hu. It is good for kidney and liver eyesight, and can also reducing urine.Raspberry contains alkaloids, flavonoids, anthraquinone, polysaccharide and other physiological active substance. Raspberry with anti-aging, regulate the reproductive system, promote cell immune function and some other pharmacological effects. So far, effect of raspberries on cardiovascular function is not clear. Use SD rats and rabbits as the object of study, to observe the effect of ethanol extracts of raspberry on hemodynamics and vascular relaxation. The purpose was to ascertain the hypotensive mechanism and provide scientific basis for the development and utilization of raspberry in china.Methods1. The use of isolated rat vascular function in experimental device, The tension transducer, The changes of BL-420E+biological signal acquisition and analysis computer system records the vascular tension, We perffused the isolated aortic rings of rats, and precontracted the rings with phenylephrine (PE,1×10-6mol/L), then observed the relaxant reactivity of ERC. Use various blocking agents pretreatment vascular ring, to discover effect of ERC mechanism of vasodilation.2. The determination of normal rabbits myocardial contractility and hemodynamics, through the pressure transducer to the left ventricular pressure signal input computer. Determination dynamic parameters of blood flow in rabbits by using physiological experiment system of BL-420S biological and functional value. In anesthetized rabbits after carotid artery of left ventricular cannulating, femoral artery intubation and continuous recording limb lead ECG Observation of rabbit ear vein for60minutes before and after administration heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (AP), left ventricular systolic pressure (LVSP), left ventricular diastolic pressure (LVDP), left ventricular mean pressure (LVAP), the maximum rate of rise of left ventricular pressure (+dp/dt max),the left ventricle contraction to dp/dt max interval (t-dp/dt max), the internal pressure of left ventricle decreased maximum rate (-dp/dt max).Results and Conclusions:1. ERC(1×10-7～1×10-4g/ml) relaxed PE-precontracted aortic rings in a concentration-dependent manner. The absence of vascular endothelium significantly attenuated ERC-induced vasorelaxation. L-NAME (1×10-5mol/L), a non-selective NOS inhibitor, and ODQ (1×10-5mol/L), a selective inhibitor of soluble guanylyl cyclase(sGC) significantly attenuated ERC-induced vasorelaxation. ERC increased cGMP levels in a concentration-dependent manner, while L-NAME and ODQ blocked the ERC-induced increase in cGMP levels. Ca2+-free buffer,2-APB (7.5×10-5mol/L), Gd3+(1×10-5mol/L), inhibitors of Ca+entry from external sources, and thapsigargin(1×10-6mol/L), an agent induces Ca2+store dERCetion via inhibition of sarco-/endoplasmic reticulum Ca2+ATPase, significantly attenuated ERC-induced vasorelaxation. Pretreatment of endothelium-intact aortic rings with wortmannin (1×10-7mol/L), an inhibitor of Akt, significantly attenuated the ERC-induced vasorelaxation. In addition, the pretreatment with a non-selective blocker of KCa channels, TEA (1×10-3mol/L), a large-conductance KCa channel (BKCa) blocker, iberiotoxin (1×10-7mol/L) and an intermediate-conductance KCa channel (IKca) blocker, charybdotoxin (1×10-7mol/L), markedly inhibited the ERC-induced vasorelaxation, while a selective blocker of small-conductance KCa channels), Apamin (3×10-7mol/L) and an ATP-sensitive K+channels (KATP) blocker, glibenclamide (1×10-5mol/L) had no significant effects on the relaxation. Pretreatment of aortic rings with indomethacin (1×10-5mol/L), an inhibitor of cyclooxygenase, atropine (1×10-6mol/L), an inhibitor of muscarinic receptors, or propranolol (1×10-6mol/L), a non-selective blocker of β-adrenoreceptors, had no effect on ERC-induced vasorelaxation. The present study shows that ERC induces vasorelaxation via endothelium-dependent eNOS-NO-cGMP signaling through the modification of intracellular Ca+and membrane BKCa and IKCa channels homeostasis.2. The findings of this study, ERC has a certain pharmacological effect on cardiovascular system.The rabbit heart rate, the maximum rate of rise of left ventricular pressure (dp/dt max) decreased significantly. And it can significantly decrease peripheral vascular resistance and blood pressure. But ERC in rabbits with left ventricular systolic pressure (LVSP), the left ventricular diastolic pressure (LVDP), left ventricular mean pressure (LVAP), the left ventricle contraction to dp/dt max interval (t-dp/dt max), the internal pressure of left ventricle decreased maximum rate (-dp/dt max) changes are not significantly affected. The above results show that ERC can effectively improve the heart function in rabbits, decreased myocardial contractility, heart rate, expansion of peripheral vascular, decreased peripheral resistance, reduce blood pressure in rabbits.