Tonic chemoreflex activation contributes to the elevated muscle sympathetic nerve activity in patients with chronic renal failure

Abstract

Objective: Sympathetic activation may contribute to both cardiovascular morbidity and the progression of chronic kidney disease. The role of the chemoreceptors in determining sympathetic nerve discharge in patients with chronic renal failure (CRF) is unknown. We tested the hypothesis that tonic activation of excitatory chemoreceptor afferents contributes to the elevated sympathetic activity in patients with CRF.

Methods: Utilizing a double-blind, randomized, vehicle-controlled design, we examined the effects of chemoreflex deactivation on muscle sympathetic nerve activity (MSNA). We compared effects of breathing 100% oxygen for 15 min with effects of breathing room air for 15 min in 12 stable patients with CRF and in 12 control individuals with similar age, gender, blood pressure and body mass index.

Results: The baseline MSNA was elevated significantly in the patients with CRF as compared with the control individuals (50 +/- 2 vs 42 +/- 2 bursts/min; P < 0.05). Reductions in systolic blood pressure and pulse pressure in response to the administration of 100% oxygen were significantly different from those observed during administration of room air in patients with CRF. In patients with CRF, MSNA decreased by 29 +/- 7% (P < 0.01) during hyperoxia but did not change during administration of room air (5 +/- 6%; P = NS). By contrast, neither 100% oxygen or room air changed any measures in control individuals.

Conclusions: Tonic activation of excitatory chemoreflex afferents contributes to increased efferent sympathetic activity to muscle circulation and to blood pressure control in patients with CRF. These findings may have important implications for understanding mechanisms underlying the link between CRF and cardiovascular disease.