Dysregulation of the Excitatory Renal Reflex in the Sympathetic Activation of Spontaneously Hypertensive Rat.

Chao Ye,Jing-Xiao Wang,Guo-Qing Zhu,Qi Chen,Yue-Hua Li,Yu-Ming Kang,Xiao-Li Wang,Fen Zheng

doi:10.3389/fphys.2021.673950

Chao Ye, Jing-Xiao Wang + Show 6 more

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https://doi.org/10.3389/fphys.2021.673950

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Abstract

Excessive sympathetic activation plays crucial roles in the pathogenesis of hypertension. Chemical stimulation of renal afferents increases the sympathetic activity and blood pressure in normal rats. This study investigated the excitatory renal reflex (ERR) in the development of hypertension in the spontaneously hypertensive rat (SHR). Experiments were performed in the Wistar-Kyoto rat (WKY) and SHR aged at 4, 12, and 24 weeks under anesthesia. Renal infusion of capsaicin was used to stimulate renal afferents, and thus, to induce ERR. The ERR was evaluated by the changes in the contralateral renal sympathetic nerve activity and mean arterial pressure. At the age of 4 weeks, the early stage with a slight or moderate hypertension, the ERR was more enhanced in SHR compared with WKY. The pressor response was greater than the sympathetic activation response in the SHR. At the age of 12 weeks, the development stage with severe hypertension, there was no significant difference in the ERR between the WKY and SHR. At the age of 24 weeks, the later stage of hypertension with long-term several hypertensions, the ERR was more attenuated in the SHR compared with the WKY. On the other hand, the pressor response to sympathetic activation due to the ERR was smaller at the age of 12 and 24 weeks than those at the age of 4 weeks. These results indicate that ERR is enhanced in the early stage of hypertension, and attenuated in the later stage of hypertension in the SHR. Abnormal ERR is involved in the sympathetic activation and the development of hypertension.

Highlights

Excessive sympathetic activity is closely associated with hypertension, chronic heart failure, and chronic kidney disease (Chen et al, 2015; Grassi and Ram, 2016; Cheng et al, 2019)
The dose of capsaicin at 1 nmol/min for 20 min was selected to induce excitatory renal reflex (ERR), and the vehicle for renal infusion had no significant effects on the renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP), and heart rate (HR) (Qiu et al, 2020; Ye et al, 2020; Zheng et al, 2020)
The capsaicin-induced ERR existed in the spontaneously hypertensive rat (SHR) at the ages of four, 12, and 24 weeks, indicating that the ERR is involved in the sympathetic activation and hypertension from the early stage to the sustained stage of hypertension in SHR

Summary

Introduction

Excessive sympathetic activity is closely associated with hypertension, chronic heart failure, and chronic kidney disease (Chen et al, 2015; Grassi and Ram, 2016; Cheng et al, 2019). Most of the patients with chronic kidney diseases have an excessive sympathetic activation and hypertension, which is closely related to the increased morbidity and mortality of cardiovascular events (Kaur et al, 2017). Selective removal of renal afferent fibers reduces the blood pressure and sympathetic activity in a rat model of renovascular hypertension (Lopes et al, 2020). We have shown that the chemical stimulation of kidney in normal rats with capsaicin causes an excitatory renal reflex (ERR), which results in the sympathetic activation and pressor responses (Ye et al, 2020). The renal afferent input increases the activity of some neurons in the PVN (Xu et al, 2015), and destruction of the PVN neurons abolishing the capsaicin-induced ERR (Ye et al, 2020)

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