Differential sympathetic response to lesion-induced chronic kidney disease in rabbits.

Yusuke Sata; Sandra L Burke; Anna M D Watson; Jay C Jha; Cindy Gueguen; Nina Eikelis; Kyungjoon Lim; Kristy L Jackson; Gavin W Lambert; Karin A M Jandeleit-Dahm; Kate M Denton; Murray D Esler; Markus P Schlaich; Geoffrey A Head
Abstract
Chronic kidney disease (CKD) is associated with greater sympathetic nerve activity but it is unclear if this is a kidney-specific response or due to generalized stimulation of sympathetic nervous system activity. To determine this, we used a rabbit model of CKD in which quantitative comparisons with control rabbits could be made of kidney sympathetic nerve activity and whole-body norepinephrine spillover. Rabbits either had surgery to lesion 5/6 of the cortex of one kidney by electro-lesioning and two weeks later removal of the contralateral kidney, or sham lesioning and sham nephrectomy. After three weeks, the blood pressure was statistically significantly 20% higher in conscious rabbits with CKD compared to rabbits with a sham operation, but their heart rate was similar. Strikingly, kidney nerve activity was 37% greater than in controls, with greater burst height and frequency. Total norepinephrine spillover was statistically significantly lower by 34%, and kidney baroreflex curves were shifted to the right in rabbits with CKD. Plasma creatinine and urine output were elevated by 38% and 131%, respectively, and the glomerular filtration rate was 37% lower than in sham-operated animals (all statistically significant). Kidney gene expression of fibronectin, transforming growth factor-β, monocyte chemotactic protein1, Nox4 and Nox5 was two- to eight-fold greater in rabbits with CKD than in control rabbits. Overall, the glomerular layer lesioning model in conscious rabbits produced a moderate, stable degree of CKD characterized by elevated blood pressure and increased kidney sympathetic nerve activity. Thus, our findings, together with that of a reduction in total norepinephrine spillover, suggest that kidney denervation, rather than generalized sympatholytic treatments, may represent a preferable management for CKD associated hypertension.th
Journal KIDNEY INTERNATIONAL
ISSN 1523-1755
Published 01 Oct 2020
Volume 98
Issue 4
Pages 906-917
DOI 10.1016/j.kint.2020.03.039
Type Journal Article | Research Support, Non-U.S. Gov't
Sponsorship Heart Foundation: 101325; Baker Heart and Diabetes Institute: EL1902
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