Direct conscious telemetry recordings demonstrate increased renal sympathetic nerve activity in rats with chronic kidney disease.

Ibrahim M Salman,Divya Sarma Kandukuri,Joanne L Harrison,Jacqueline K Phillips,Cara M Hildreth

doi:10.3389/fphys.2015.00218

Ibrahim M Salman, Divya Sarma Kandukuri + Show 3 more

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https://doi.org/10.3389/fphys.2015.00218

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Abstract

Chronic kidney disease (CKD) is associated with sympathetic hyperactivity and impaired blood pressure control reflex responses, yet direct evidence demonstrating these features of autonomic dysfunction in conscious animals is still lacking. Here we measured renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) using telemetry-based recordings in a rat model of CKD, the Lewis Polycystic Kidney (LPK) rat, and assessed responses to chemoreflex activation and acute stress. Male LPK and Lewis control animals (total n = 16) were instrumented for telemetric recording of RSNA and MAP. At 12–13 weeks-of-age, resting RSNA and MAP, sympathetic and haemodynamic responses to both peripheral (hypoxia: 10% O2) and central chemoreflex (hypercapnia: 7% CO2) activation and acute stress (open-field exposure), were measured. As indicators of renal function, urinary protein (UPro) and creatinine (UCr) levels were assessed. LPK rats had higher resting RSNA (1.2 ± 0.1 vs. 0.6 ± 0.1 μV, p < 0.05) and MAP (151 ± 8 vs. 97 ± 2 mmHg, p < 0.05) compared to Lewis. MAP was negatively correlated with UCr (r = −0.80, p = 0.002) and positively correlated with RSNA (r = 0.66, p = 0.014), with multiple linear regression modeling indicating the strongest correlation was with Ucr. RSNA and MAP responses to activation of the central chemoreflex and open-field stress were reduced in the LPK relative to the Lewis (all p < 0.05). This is the first description of dual conscious telemetry recording of RSNA and MAP in a genetic rodent model of CKD. Elevated RSNA is likely a key contributor to the marked hypertension in this model, while attenuated RSNA and MAP responses to central chemoreflex activation and acute stress in the LPK indicate possible deficits in the neural processing of autonomic outflows evoked by these sympathoexcitatory pathways.

Highlights

Sympathetic nervous system (SNS) hyperactivity is synonymous with chronic kidney disease (CKD), contributing to hypertension, renal disease progression, and consequent cardiovascular morbidity and mortality (Penne et al, 2009; Grassi et al, 2011)
urinary protein (UPro) and UPC were not significantly correlated with mean arterial pressure (MAP) and were both excluded from the final model
The level of renal sympathetic nerve activity (RSNA) recorded following administration of hexamethonium was not different between Lewis and Lewis Polycystic Kidney (LPK) and in both groups was comparable to that recorded following euthanasia [Lewis: 1.5 ± 0.2 (n = 8) vs. 1.3 ± 0.2 (n = 9) μV and LPK: 1.6 ± 0.2 (n = 4) vs. 1.3 ± 0.2 (n = 7) μV, hexamethonium vs. euthanasia; all p > 0.05]. This is the first description of conscious concurrent telemetric recordings of RSNA and blood pressure in a genetic rodent model of CKD

Summary

Introduction

Sympathetic nervous system (SNS) hyperactivity is synonymous with chronic kidney disease (CKD), contributing to hypertension, renal disease progression, and consequent cardiovascular morbidity and mortality (Penne et al, 2009; Grassi et al, 2011). Plasma catecholamine levels (Zoccali et al, 2002; Grassi et al, 2011) and renal noradrenaline spillover (Schlaich et al, 2013) are increased, and direct measurements of muscle sympathetic nerve activity (SNA) reveal elevated tonic levels (Neumann et al, 2007; Grassi et al, 2011; Schlaich et al, 2013). Measurement of plasma catecholamine levels can reveal global activity but not the discrete contributions of organ-specific sympathetic nerve beds and noradrenaline spillover studies, while organ specific, must take into consideration SNA and altered neurotransmitter uptake as an underlying mechanism. For example responses to the ganglionic blocker hexamethonium have been shown to have different responses on sympathetic control of blood pressure in anesthetized vs. conscious animals, in both normotensive and hypertensive models (Biancardi et al, 2007)

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