Contribution of the Renal Nerves to Hypertension in a Rabbit Model of Chronic Kidney Disease. Issue 5 (November 2020)

• Record Type: Journal Article
• Authors: Sata, Yusuke; Burke, Sandra L.; Gueguen, Cindy; Lim, Kyungjoon; Watson, Anna M.D.; Jha, Jay C.; Eikelis, Nina; Jackson, Kristy L.; Lambert, Gavin W.; Denton, Kate M.; Schlaich, Markus P.; Head, Geoffrey A.
• Is Part Of: Hypertension. Volume 76:Issue 5(2020)
• Publication Date: 2020-11
• Subjects: blood pressure -- hypertension -- rabbits -- renal insufficiency, chronic -- sympathetic nervous system; Hypertension -- Periodicals; Hypertension -- Treatment -- Periodicals; 616.132005
• DOI: 10.1161/HYPERTENSIONAHA.120.15769
• Languages: English
• ISSNs: 0194-911X

Abstract

Abstract : Overactivity of the sympathetic nervous system and high blood pressure are implicated in the development and progression of chronic kidney disease (CKD) and independently predict cardiovascular events in end-stage renal disease. To assess the role of renal nerves, we determined whether renal denervation (RDN) altered the hypertension and sympathoexcitation associated with a rabbit model of CKD. The model involves glomerular layer lesioning and uninephrectomy, resulting in renal function reduced by one-third and diuresis. After 3-week CKD, blood pressure was 13±2 mm Hg higher than at baseline ( P <0.001), and compared with sham control rabbits, renal sympathetic nerve activity was 1.2±0.5 normalized units greater ( P =0.01). The depressor response to ganglion blockade was also +8.0±3 mm Hg greater, but total norepinephrine spillover was 8.7±3.7 ng/min lower (both P <0.05). RDN CKD rabbits only increased blood pressure by 8.0±1.5 mm Hg. Renal sympathetic activity, the response to ganglion blockade and diuresis were similar to sham denervated rabbits (non-CKD). CKD rabbits had intact renal sympathetic baroreflex gain and range, as well as normal sympathetic responses to airjet stress. However, hypoxia-induced sympathoexcitation was reduced by −9±0.4 normalized units. RDN did not alter the sympathetic response to hypoxia or airjet stress. CKD increased oxidative stress markers Nox5 and MCP-1 (monocyte chemoattractant protein-1) in the kidney, but RDN had no effect on these measures. Thus, RDN is an effective treatment for hypertension in this model of CKD without further impairing renal function or altering the normal sympathetic reflex responses to various environmental stimuli. Graphic Abstract—: A graphic abstract is available for this article. Abstract : Supplemental Digital Content is available in the text.