The Role Of PI3k/Akt Pathway In Vasodilation Induced By Puerarin

Puerarin(Pue)is one new isoflavones extracted from the root of kudzu vine.Studies have confirmed that Pue shows many pharmacological activities,such as cardiovascular protection,anti osteoporosis,anti liver injury,hypoglycemic effects,neuroprotection,immunoregulation and so on.However,the possible mechanisms of hypotension and vasodilation induced by Pue is not clear.Hypertension can cause can cause secondary functional or organic damages,such as heart,blood vessels,brain and kidney etc.To develop more specific antihypertensive drugs has always been the research focus of related subjects.Nitric oxide(nitric oxide,NO)is one of the most important physiological factors in the homeostasis regulation of blood pressure,which is synthesized by endothelial nitric oxide synthase(eNOS).The purpose of this study was to investigate the effects of Pue on isolated aortic rings in spontaneously hypertensive rats(SHR)by in vitro arterial perfusion and molecular biological techniques and explore the possible underlying molecular mechanisms.Objective: To investigate the effects of Pue on thoracic aorta vasodilatation and the possible mechanisms in SHR.Methods: Twelve weeks old male WKY rats and SHR were used in this research.The vasodilatation of thoracic aorta was recorded by using organ bath technique and PowerLab biological function experiment system.The levels of eNOS protein expression were determined by using Western blot.The level of NO in local tissue was determined by ELISA.Results:1.Pue could induce the vasodilatation of thoracic aorta in WKY rats and SHR dose-dependently(P < 0.05).The effects on SHR was more significant than that of WKY rats(P < 0.05).The effects of Pue could be partially blocked by de-endothelium or L-NAME pretreatment.2.Pue increased the expression of eNOS in thoracic aorta tissue of WKY rats and SHR(P < 0.05),and increased the local NO level in a concentration dependent manner in SHR(P < 0.05).The effects on SHR was more significant than that of WKY rats(P < 0.05).3.Pretreatment with MEK/ERK signal pathway blocker PD98059 and PKA /cAMP pathway blocker H89 had no effects on Pue-induced vasodilatation of thoracic aorta andactivation of local eNOS.4.Pretreatment with LY294002,the PI3 K pathway inhibiter,could block the Pue induced vasodilatation and eNOS activation in thoracic aorta of SHR(P<0.05).Conclusions: Pue could induce vasodilation of thoracic aorta by activated eNOS via PI3K/Akt pathway in SHR.