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

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.

Augmented Respiratory–Sympathetic Coupling and Hemodynamic Response to Acute Mild Hypoxia in Female Rodents With Chronic Kidney Disease

“…Another consideration is that our sympathetic nerve recording data analysis is reported as absolute value microvolt recordings from multifiber sympathetic nerve preparations. While differences in the contact between the nerve and electrode can result in differences in the microvolt signal amplitude, our work, in this study and previously under both conscious (Salman et al, 2015a) and anesthetized conditions (Yao et al, 2015;Saha et al, 2019), demonstrated SNA at baseline was heightened in the LPK model with a low level of variance within each group of animals. This is consistent with the work of others who similarly report SNA data when comparing baseline activity between different groups of animals (Guild et al, 2010;Stocker and Muntzel, 2013;Burke et al, 2016;Ong et al, 2019) and, importantly, as presented in the seminal study in this field by Simms et al (2009), who used microvolt data to measure respiratory and sympathetic responses to changes in chemoreceptor stimuli in the SHR rat.…”

Blunted natriuretic response to saline loading in sheep with hypertensive kidney disease following radiofrequency catheter-based renal denervation

“…Compared with normotensive counterparts, elevations in basal RSNA are present in the SHR (demonstrated by direct nerve recording) 39 , and in patients with essential hypertension (demonstrated by increased renal norepinephrine spillover) 40 . There is also evidence for elevated RSNA in chronic kidney disease 41 – 44 . Although we have not directly measured RSNA in the sheep with hypertensive CKD, we have demonstrated hyperinnervation of renal efferent sympathetic and renal afferent sensory nerves together with enhanced vascular contraction to renal nerve stimulation 28 , 45 .…”

Gut microbiota and inflammation in chronic kidney disease and their roles in the development of cardiovascular disease

“…Conversely, the species found to be decreased in CKD are among those that strengthen gut barrier function [16,36,37]; produce anti-inflammatory [46,71,73,109], NO [16,47], CDCA, UDCA [50,[83][84][85], GABA [60,61,110], Ach [65,107,108], and the vitamin B complex [17, 52-54, 81, 82]; increase the production of gut hormones with anti-inflammatory properties [57][58][59][76][77][78][79]; increase anti-inflammatory vagal activity [90,93,97]; and decrease pro-inflammatory renal sympathetic activity. Interestingly, CKD is associated with gut barrier dysfunction, an increase in uremic toxins [101], elevated renal sympathetic activity [111], lower group B vitamin levels [112][113][114] and NO [115], and a reduction in vagal activity [116], which may stem from the gut dysbiosis found in patients with CKD. Therefore, we can suggest that a healthy gut microbiota can protect from CKD, whereas gut dysbiosis takes part in the development and progression of CKD through a number of pathways that manipulate host inflammatory activity.…”