Effect Of RDN On Glu And GABA Of Rostral Ventrolateral Medulla In Hypertensive Canines

Objective:To investigate the change of blood pressure, serum AngII, glutamate (Glu), gamma amino acid butyric acid (GABA), glutamic acid decarboxylase65(GAD65), type1angiotensin Ⅱ receptor (AT1R) of rostral ventrolateral medulla (RVLM) following catheter-based renal denervation (RDN) in hypertensive Canine model. Secondarily, we observed the effect of RDN on Glu and GABA of RVLM and the possible antihypertensive mechanism in hypertensive canine.Methods:1.Twenty-eight Beagles (10-12months old) were divided into control group (n=6) and model group (n=22). Hypertension model was established by feeding anlmals with high fat diet for12weeks.2. After hypertension model was established, animals were randomized into RDN group (renal denervation, n=10) and sham group (renal angiography, n=10).3.Body weight, blood pressure, and blood specimens were measured at baseline, pre-procedure (12weeks after modelling), and6month post-procedure. All animals were sacrificed at6months after procedure and rostral ventrolateral medulla were obtained.4. Serum Ang Ⅱ level was measured with radioimmunoassay method; Glu and GABA concentration were measured with hgh-performance liquid chromatogaphy; The expression of GAD65was examined with real-time PCR, western-blot and immunohistochemical staining; The expression of AT1R was measured with real-time PCR and western-blot.Results:1. After12weeks of modeling, compared to baseline and the control group, the body weight, SBP, DBP and MAP significantly increased in model group (P<0.05).2. Postprocedurally, compared to the pre-procedure and the sham group, the SBP, DBP, and MAP of RDN group were significantly lower (P<0.05); In sham group, these indices were found significantly higher of sham-operation groups than control group at each time points.3.Compared to sham group, the Glu level of RVLM was significantly lower whereas the GABA level and GAD65were significantly higher in RDN group (all p<0.05); Serum AngⅡ level and the expression of ATIR in RDN group were significantly lower than sham group.4. GABA and GAD65were positively correlated (p<0.05); Glu and serum AngⅡ were positively correlated (p<0.05); GABA and serum AngⅡ were negatively correlated (p<0.05).Conclusions:Renal denervation reduced Glu level and increased GABA level of RVLM by increasing the expression of GAD65and decreasing the serum AngⅡ level, which may be related with the antihypertensive effect of RDN.