Renal Denervation Improves the Baroreflex and GABA System in Chronic Kidney Disease-induced Hypertension

• Published in: Scientific reports Vol. 6; no. 1; p. 38447
• Main Authors: Chen, Hsin-Hung, Cheng, Pei-Wen, Ho, Wen-Yu, Lu, Pei-Jung, Lai, Chi-Cheng, Tseng, Yang-Ming, Fang, Hua-Chang, Sun, Gwo-Ching, Hsiao, Michael, Liu, Chun-Peng, Tseng, Ching-Jiunn
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 05.12.2016
• Subjects: Ablation; Animals; Baclofen; Baroreceptors; Baroreflex - drug effects; Baroreflex - physiology; Blood pressure; Blood Pressure - drug effects; Cerebrospinal fluid; Denervation; Denervation - methods; Gabapentin; Glutamate decarboxylase; Glutamic acid; Heart diseases; Humans; Hypertension; Hypertension - complications; Hypertension - metabolism; Hypertension - physiopathology; Hypertension - therapy; Hypertension, Renal - metabolism; Hypertension, Renal - physiopathology; Hypertension, Renal - therapy; Kidney - drug effects; Kidney - innervation; Kidney - physiopathology; Kidney diseases; Kidneys; Nephrectomy; Nephrectomy - adverse effects; Nephritis - metabolism; Nephritis - physiopathology; Nephritis - therapy; Neurons, Afferent - drug effects; Phenol - adverse effects; Rats; Receptors, GABA-B - metabolism; Reflexes; Renal artery; Renal function; Renal Insufficiency, Chronic - complications; Renal Insufficiency, Chronic - metabolism; Renal Insufficiency, Chronic - physiopathology; Renal Insufficiency, Chronic - therapy; Rodents; Sensory neurons; Solitary Nucleus - metabolism; Solitary Nucleus - physiopathology; Solitary tract nucleus; Sympathetic nerves; γ-Aminobutyric acid B receptors
• DOI: 10.1038/srep38447
• ISSN: 2045-2322

Hypertensive rats with chronic kidney disease (CKD) exhibit enhanced gamma-aminobutyric acid (GABA) receptor function and regulation within the nucleus tractus solitarii (NTS). For CKD with hypertension, renal denervation (RD) interrupts the afferent renal sympathetic nerves, which are connecting to the NTS. The objective of the present study was to investigate how RD improves CKD-induced hypertension. Rats underwent 5/6 nephrectomy for 8 weeks, which induced CKD and hypertension. RD was induced by applying phenol to surround the renal artery in CKD. RD improved blood pressure (BP) by lowering sympathetic nerve activity and markedly restored the baroreflex response in CKD. The GABA receptor expression was increased in the NTS of CKD; moreover, the central GABA levels were reduced in the cerebrospinal fluid, and the peripheral GABA levels were increased in the serum. RD restored the glutamic acid decarboxylase activity in the NTS in CKD, similar to the effect observed for central treatment with baclofen, and the systemic administration of gabapentin reduced BP. RD slightly improved renal function and cardiac load in CKD. RD may improve CKD-induced hypertension by modulating the baroreflex response, improving GABA system dysfunction and preventing the development and reducing the severity of cardiorenal syndrome type 4 in CKD rats.