Renal sympathetic denervation lowers arterial pressure in canines with obesity-induced hypertension by regulating GAD65 and AT₁R expression in rostral ventrolateral medulla

Abstract

To explore the roles of glutamate acid decarboxylase 65 (GAD65) and angiotensin II type 1 receptor (ATR) in the action of renal sympathetic denervation (RSD) on obesity-induced hypertension in canines. Thirty-two beagles were randomly divided into a hypertensive model (n = 22) and control (n = 10) groups. A hypertensive canine model was established by feeding a high-fat diet. Twenty hypertensive beagles were randomized equally to a sham-surgery and RSD-treated group receiving catheter-based radiofrequency RSD. Compared with the control group, the sham-surgery group exhibited significant increases in blood pressure, serum angiotensin II level, rostral ventrolateral medulla (RVLM) glutamate level, and ATR mRNA and protein expression and decreases in γ-amino acid butyric acid (γ-GABA) level and GAD65 mRNA and protein expression in the RVLM (all P < 0.05). Treatment with RSD significantly attenuated the above abnormal alterations (all P < 0.05). Linear correlation analysis revealed that angiotensin II level was positively correlated with glutamate level (r = 0.804) and inversely correlated with γ-GABA level (r = -0.765). GAD65 protein expression was positively correlated with γ-GABA level (r = 0.782). Catheter-based radiofrequency RSD can decrease blood pressure in obesity-induced hypertensive canines. The antihypertensive mechanism might be linked to upregulation of GAD65 and downregulation of ATR in the RVLM.