The Study Of Effect Of Cannabinoid-type Receptor On The Pathogenesis Of Spontaneously Hypertensive Rats In Rostral Ventrolateral Medulla

Hypertension is a common cardiovascular disease in humans.Hypertensive patients almost geometric progression growth in 50 years and it has become the biggest public health problem worldwide.Although many scholars have studied the pathogenesis of hypertension from various aspects,there are still 90% causes of hypertensive patients unclear.Long-term high blood pressure can lead to chronic damages of heart,brain,kidney and other important organs,which seriously endangers people's health.Therefore,how to control high blood pressure,reduce morbidity and mortality of cardiovascular and cerebrovascular diseases,improve people's quality of life is a major medical problem to be solved at present.The rostral ventrolateral medulla(RVLM)is the main source of sympathetic excitability and one of the important parts of the central nervous system.Basic research shows that the sympathetic center excitability increased in hypertension is mainly related to the tonic activity of the anterior sympathetic neurons in RVLM region.The axons of RVLM neurons are through the inside of medulla oblongata,and directly reach the sympathetic peganglinoic neurons in the medial lateral column of thoracic lumbar spinal cord,Which is the last control center of blood pressure.Cannabinoid type 1 receptors(CB1R)are highly expressed in the forebrain,basal nucleus,cerebellum,hippocampus and cerebral cortex,and have a closed relationship with various physiological activities such as obesity,dyslipidemia,hypertension,pain and diabetes mellitus etc.Presynaptic CB1 receptors in various neurons regulate multiple neurotransmitters release.Spontaneously hypertensive rats(SHR)have stable hypertensive heredity–that was cultivated from Wistar rats by Aoki and Okamoto.SHR's bloodpressure increased with the age.Hypertension is established in 3 or 4 months,and blood pressure rises to the peak value in 6 months.And the general level of adult rats blood pressure is higher than 200 mm Hg.Therefore,SHR is an ideal animal model for hypertension research,pathology,physiology,pharmacology and other aspects.In this study,male SHR were used as the research object to explore the potential regulation mechanism of cannabinoid system in RVLM.Purposes:1 To study that stimulation of cannabinoid type 1(CB1)receptor in the rostral ventrolateral medulla(RVLM)effects the cardiovascular function.2 To detect CB1R expression of RVLM in SHR and Wistar,and CB1R expression in catecholamine neurons,glutamate or GABA neurons in RVLM.Methods:1 SHR or Wistar rats were anesthetized,we keep tracheal intubation for mechanical ventilation,while recording the left renal sympathetic nerve discharge and blood pressure.RVLM microinjection experiments were performed to observe effects of ACEA and AM251 on artery blood pressure and renal sympathetic activity.2 Using western blot and immunocytochemical staining technique to detect the expression of CB1R in RVLM region of SHR and Wistar rats.3 The expression of CB1R in RVLM region of SHR and Wistar rats was detected by immunofluorescence.The co-localization of CB1R and glutamatergic neurons,catecholamine neurons or GABA neurons were observed by immunocytochemical double staining technique.Results:1 Under the basic condition,the arterial blood pressure of SHR was significantly higher than that of Wistar rats.Microinjection of ACEA(10?mol/L,100?mol/L,1mmol/L),selective cannabinoid-type1 receptor agonists,into SHR and Wistar rats RVLM can dose-dependently increase blood pressure and renal sympathetic nerve activity.And the increased blood pressure of SHR rats were significantly higher than that of Wistar rats.Moreover,these effects were abolished by pre-administrations of AM251(10?mol/L)into the RVLM.2 Western blot experiment and immunofluorescence technique shows that the expression of CB1R in RVLM of SHR rats was significantly higher than that of Wistar rats.3 Immunocytochemical double staining technique showed that CB1R and catecholamine neurons,glutamatergic neurons or GABA neurons are co-localized situation,Revealing that CB1R are expressed in catecholamine neurons,glutamatergic neurons and GABA neurons.Conclusions:The enhancement of CB1R in RVLM area of spontaneous hypertensive rats induces the central exciting,peripheral sympathetic nerve excitement and vasoconstriction,which leads to the hypertension.