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

Abstract

Hypertensive rats with chronic kidney disease (CKD) exhibit enhanced gamma-aminobutyric acid (GABA) B 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 B 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.Hypertension occurs in more than 80% of patients with chronic kidney disease (CKD) 1 . Patients with CKD have a higher risk of developing cardiovascular diseases than the general population 2,3 . Multiple guidelines discuss the importance of lowering blood pressure (BP) to slow the progression of renal disease and reduce cardiovascular morbidity and mortality 4 . However, to achieve and maintain adequate BP control, most patients with CKD require multiple antihypertensive agents. Despite the increasing prevalence of CKD-induced hypertension, the awareness of hypertension among individuals with CKD remains suboptimal, and the rates of BP control remain poor 5 . Recently, many studies have provided evidence that renal denervation (RD) has beneficial effects in patients with CKD-induced hypertension 6 . However, RD improves CKD progression through unknown mechanisms.

Differences in Serum Amino Acid Phenotypes Among Patients with Diabetic Nephropathy, Hypertensive Nephropathy, and Chronic Nephritis

“…GABA has been reported to reduce cerebrospinal fluid in hypertensive CKD rats, and oral administration of a GABA analog increased periphery GABA levels and decreased blood pressure [28]. Consistent with this animal research, we found that GABA levels were negative correlated with blood pressure in CKD patients, suggesting that GABA supplementation may be beneficial in CKD patients with hypertension.…”

Electroacupuncture Improves Baroreflex and γ-Aminobutyric Acid Type B Receptor-Mediated Responses in the Nucleus Tractus Solitarii of Hypertensive Rats

“…It has been suggested that arterial baroreflex is involved in the long-term control of BP [ 30 ]. Several studies have shown that the sensitivity of the baroreflex is diminished in several forms of hypertension [ 22 , 31 , 32 ]. In addition, patients with baroreflex failure suffer from a volatile hypertension with sympathetic nerve activity increased for years [ 33 ].…”

Cooperative Oxygen Sensing by the Kidney and Carotid Body in Blood Pressure Control

“…Similarly, in patients with renovascular hypertension, restoration of renal perfusion reduces muscle sympathetic nerve activity and blood pressure (Miyajima et al, 1991 ) and renal nerve ablation can reduce blood pressure and muscle sympathetic nerve activity in some patients with resistant hypertension (Hering et al, 2014 ). Finally, given the change in set-point of sympathetic activity and blood pressure it is perhaps not surprising that the baroreceptor reflex is reset and gain improved following renal denervation in a rat model of chronic kidney disease (Chen et al, 2016 ).…”