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 (AT₁R) 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 AT₁R 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 AT₁R in the RVLM.

KEYWORDS:

• AT₁R
• GAD65
• gamma amino acid butyric acid
• hypertension
• renal sympathetic denervation
• rostral ventrolateral medulla

Declaration of interest

The authors declare that they have no conflict of interest.

Funding

This work was funded by the Fundamental Research Funds for the Central Universities of Central South University (2016zzts159).

The experimental protocols were approved by the Institutional Animal Care and Use Committee of Department of Cardiology, The Third Xiangya Hospital of Central South University. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

Additional information

Funding

This work was funded by the Fundamental Research Funds for the Central Universities of Central South University (2016zzts159). The experimental protocols were approved by the Institutional Animal Care and Use Committee of Department of Cardiology, The Third Xiangya Hospital of Central South University. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.