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. 2017 Mar 2;6(3):e004716.
doi: 10.1161/JAHA.116.004716.

Impacts of Renal Sympathetic Activation on Atrial Fibrillation: The Potential Role of the Autonomic Cross Talk Between Kidney and Heart

Lilei Yu  1   2   3 , Bing Huang  1   2   3 , Zhuo Wang  1   2   3 , Songyun Wang  1   2   3 , Menglong Wang  1   2   3 , Xuefei Li  1   2   3 , Liping Zhou  1   2   3 , Guannan Meng  1   2   3 , Shenxu Yuan  1   2   3 , Xiaoya Zhou  1   2   3 , Hong Jiang  4   2   3
Affiliations

Impacts of Renal Sympathetic Activation on Atrial Fibrillation: The Potential Role of the Autonomic Cross Talk Between Kidney and Heart

Lilei Yu et al. J Am Heart Assoc. .

Abstract

Background: Recent studies have demonstrated that there is a high variability of renal sympathetic nerve density distribution from proximal to distal renal artery segments. The aim of our study was to investigate the roles of renal sympathetic nerve stimulation (RSS) on atrial fibrillation and cardiac autonomic nervous activity.

Methods and results: Twenty-eight dogs were randomly assigned to the proximal RSS group (P-RSS, N=7), middle RSS group (M-RSS, N=7), distal RSS group (D-RSS, N=7), and the control group (sham RSS, N=7). RSS was performed using electrical stimulation on the bilateral renal arteries for 3 hours. Effective refractory period and the window of vulnerability were measured at atrial and pulmonary veins sites. Superior left ganglionated plexi (SLGP) and left stellate ganglion (LSG) function and neural activity were determined. C-fos and nerve growth factor protein expression in the SLGP and LSG were examined. Only P-RSS (1) caused pronounced blood pressure rises, induced a significant decrease in effective refractory period, and generated a marked increase in cumulative window of vulnerability and effective refractory period dispersion; (2) increased the frequency and amplitude of the neural activity in the SLGP and LSG; (3) increased SLGP and LSG function; and (4) upregulated the level of c-fos and nerve growth factor expression in the SLGP and LSG.

Conclusions: This study demonstrated that renal sympathetic nerve activation induced by 3 hours of P-RSS facilitated atrial fibrillation inducibility by upregulating cardiac autonomic nervous activity, suggesting a potential autonomic cross talk between kidney and heart.

Keywords: atrial fibrillation; ganglionated plexus; left stellate ganglion; renal sympathetic nervous system.

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Figures

Figure 1
Figure 1
Schematic representation of location of the electrode on the adventitia of the renal artery. D‐RSS indicates distal RSS; M‐RSS, middle RSS; P‐RSS, proximal RSS; RSS, renal sympathetic stimulation.
Figure 2
Figure 2
Changes in blood pressure (BP). A, Effects of immediate renal sympathetic stimulation (RSS) on BP. B, effects of 3 hours (3H) of RSS on BP. BS indicates baseline; Ctr, control; D‐RSS, distal RSS; M‐RSS, middle RSS; P‐RSS, proximal RSS. *P<0.05 vs baseline (BS); # P<0.05 vs other 3 groups at the same time point.
Figure 3
Figure 3
Effective refractory periods (ERP), ERP dispersion, and cumulative window of vulnerability (ΣWOV) changes in 4 groups. BS indicates baseline; Ctr, control; D‐RSS, distal RSS; M‐RSS, middle RSS; P‐RSS, proximal RSS; RA and LA, right and left atria; RAA and LAA, right and left atrial appendage; RIPV and LIPV, right and left inferior pulmonary vein; RSPV and LSPV, right and left superior pulmonary vein; RSS, renal sympathetic stimulation; 1H, 2H, 3H indicate 1, 2, and 3 hours of RSS, respectively. *P<0.05 vs BS; # P<0.05 vs other 3 groups at the same time point.
Figure 4
Figure 4
Representative examples (A and B) and quantification analysis (C and D) of autonomic neural activity in 4 groups. A and C, Neural activity in superior left ganglionated plexi (SLGP). (B and D, neural activity in left stellate ganglion (LSG). BS indicates baseline; Ctr, control; D‐RSS, distal RSS; M‐RSS, middle RSS; P‐RSS, proximal RSS; RSS, renal sympathetic stimulation. *P<0.05 vs baseline (BS); # P<0.05 vs other 3 group at the same time point.
Figure 5
Figure 5
Changes of autonomic neural function by RSS in 4 groups. A, Sinus rate (SR) change induced by superior left ganglionated plexus (SLGP) stimulation. B systolic blood pressure (BP) change induced by left stellate ganglion (LSG) stimulation. BS indicates baseline; Ctr, control; D‐RSS, distal RSS; M‐RSS, middle RSS; P‐RSS, proximal RSS.; RSS, renal sympathetic stimulation. *P<0.05 vs baseline (BS).
Figure 6
Figure 6
The relative messenger RNA (mRNA) levels of c‐fos and nerve growth factor (NGF) expression in superior left ganglionated plexi (SLGP) (A and C) and left stellate ganglion (LSG) (B and D). BS indicates baseline; Ctr, control; D‐RSS, distal RSS; M‐RSS, middle RSS; P‐RSS, proximal RSS; RSS, renal sympathetic stimulation. *P<0.05 vs other 3 groups at the same time point.
Figure 7
Figure 7
Representative examples (A and B) and relative protein levels (C and D) of c‐fos and NGF expression in superior left ganglionated plexi (SLGP) (A and B) and left stellate ganglion (LSG). BS indicates baseline; Ctr, control; D‐RSS, distal RSS; M‐RSS, middle RSS; P‐RSS, proximal RSS; RSS, renal sympathetic stimulation. *P<0.05 vs other 3 groups at the same time point.
Figure 8
Figure 8
Schematic summary of potential cardiorenal neuraxial pathways through which activation of renal sympathetic nerve (RSN) could influence the atrium. Activation of RSN increases input to the nucleus of the solitary tract (NTS) in the medulla and influences the activity of NTS neurons projecting to the cardiac autonomic nervous system, thereby increasing the nerve activity of the atrial ganglionated plexi (GP) and the left stellate ganglion (LSG). Increased GP and LSG neural activities have been proved to contribute to the initiation and maintenance of atrial fibrillation (AF).7, 8, 9, 10
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