Respiratory sympathetic modulation is augmented in chronic kidney disease

TL;DR

This study demonstrates that respiratory modulation of sympathetic nerve activity is heightened in a rodent model of chronic kidney disease, especially during hypoxia, potentially contributing to hypertension development.

Contribution

It reveals that respiratory sympathetic modulation is augmented in CKD, providing new insights into its role in hypertension pathogenesis in this disease model.

Findings

RespSNA was increased in CKD rats compared to controls.

Hypoxia and hypercapnia elicited greater respSNA responses in CKD rats.

Enhanced respSNA may contribute to hypertension in CKD.

Abstract

Respiratory modulation of sympathetic nerve activity (respSNA) was studied in a hypertensive rodent model of chronic kidney disease (CKD) using Lewis Polycystic Kidney (LPK) rats and Lewis controls. In adult animals under in vivo anaesthetised conditions (n=8-10/strain), respiratory modulation of splanchnic and renal nerve activity was compared under control conditions, and during peripheral (hypoxia), and central, chemoreceptor (hypercapnia) challenge. RespSNA was increased in the LPK vs. Lewis (area under curve (AUC) splanchnic and renal: 8.7$\pm$1.1 vs. 3.5$\pm$0.5 and 10.6$\pm$1.1 vs. 7.1$\pm$0.2 $\mu$V.s, respectively, P<0.05). Hypoxia and hypercapnia increased respSNA in both strains but the magnitude of the response was greater in LPK, particularly in response to hypoxia. In juvenile animals studied using a working heart brainstem preparation (n=7-10/strain), increased respSNA was evident in the LPK (thoracic SNA, AUC: 0.86$\pm$0.1 vs. 0.42$\pm$0.1 $\mu$V.s, P<0.05), and activation of peripheral chemoreceptors (NaCN) again drove a larger increase in respSNA in the LPK with no difference in the response to hypercapnia. Amplified respSNA occurs in CKD and may contribute to the development of hypertension.