Effect Of Reineckiagenin On Contractile Function Of Isolated Thoracic Aorta In Spontaneously Hypertensive Rats

Reineckiagenin(REI)is an effective monomer component which is isolated from the raw Reineckiagenin.Researches have provend that reineckiagenin genus is a phytoestrogen with estrogen-like activity,and articles have pointed out that reineckiagenin has the anti-inflammatory effect.However,there are few studies on its cardiovascular function,and its specific mechanism of lowering blood pressure and diastolicing blood vessels are not clear.Hypertension is a common clinical disease with high mortality and disability.In addition,hypertension is also an independent risk factor for stroke,coronary heart disease,heart failure,renal insufficiency,peripheral vascular disease,early death,and many other major diseases.The development of safer and more effective antihypertensive drugs has always been the focus of multidisciplinary researches.Nitric oxide(NO)is one of the vasodilators(EDRF)secreted by endothelial cells and is involved in the physiological regulation of blood pressure.Endothelial nitric oxide synthase(e NOS)expressed by vascular endothelial cells is an important synthetase of NO in the cardiovascular system.e NOS is activated through three signaling pathways: MEK / ERK,PI3 K / Akt,and c AMP / PKA pathways.The purpose of this study is to treat reineckiagenin with spontaneously hypertensive rat(SHR)in a classic hypertensive animal model,and use functional and molecular biology techniques to treat tissue and protein expression in vitro.At different levels,the effects of reineckiagenin on thoracic aortic diastolic function in SHR rats and its possible mechanism were explored.Objective: To observe the effect of reineckiagenin on the diastolic function of isolated thoracic aorta in SHR,and to explore its possible molecular mechanism.Methods: 11-week-old male SHR rats were matched with SHR-matched normal blood pressure rats(Wistar-Kyoto,WKY).The isolated vascular ring perfusion device and Power Lab data acquisition system were used to record the aortic ring diastolic activity of each group of rats.Western blot was used to determine the expression of e NOS protein invascular tissues,and ELISA kit was used to detect the level of NO in vascular tissues.The result: 1.REI can induce the relaxation of isolated thoracic aortic rings in spontaneously hypertensive rats(SHR)and control rats(WKY)in a dose-dependent manner,and the relaxation effect on SHR thoracic aorta is significantly stronger than WKY.Endothelial removal of blood vessels or pretreatment with nitric oxide synthase inhibitor L-NAME can largely block the vasodilation effect of reineckiagenin.2.REI can significantly increase the expression level of e NOS in rat thoracic aorta tissue,and increase the concentration of NO in local tissues in a concentration-dependent manner,and has a stronger effect on SHR than WKY.3.Pretreatment with PD98059,a blocker of MEK / ERK pathway,had no effect on the expression of e NOS in isolated thoracic aortic rings and activated local vascular tissues of REI dilated SHR rats.4.Pretreatment with H89,a PKA / c AMP pathway blocker,had no effect on the expression of e NOS in SHR local vascular tissues after REI activation.5.Pretreatment with PI3 K / Akt pathway blocker LY294002 could largely block REI activation of e NOS in local tissues of isolated thoracic aortic rings in SHR rats(P <0.05).Conclusions: Reineckiagenin activate e NOS expression in endothelial cells through the PI3 K / Akt pathway,increase NO levels in local tissues,and induce relaxation of isolated thoracic aorta in SHR rats.