Chemical Stimulation of Renal Tissue Induces Sympathetic Activation and a Pressor Response via the Paraventricular Nucleus in Rats

Abstract

Sympathetic activation and the kidney play critical roles in hypertension and chronic heart failure. The role of the kidney in sympathetic activation is still not well known. In this study, we revealed an excitatory renal reflex (ERR) in rats induced by chemical stimulation of the kidney that regulated sympathetic activity and blood pressure. The ERR was induced by renal infusion of capsaicin, and evaluated by the changes in renal sympathetic outflow, blood pressure, and heart rate. Renal infusion of capsaicin dose-dependently increased the contralateral renal sympathetic nerve activity, mean arterial pressure, and heart rate. Capsaicin in the corticomedullary border had greater effects than in the cortex or medulla. Intravenous infusion of capsaicin had no significant effects. The effects of renal infusion of capsaicin were abolished by ipsilateral renal denervation, but were not affected by bilateral sinoaortic denervation. Renal infusion of capsaicin increased the ipsilateral renal afferent activity. The ERR was also induced by renal infusion of bradykinin, adenosine, and angiotensin II, but not by ATP. Renal infusion of capsaicin increased c-Fos expression in the paraventricular nucleus (PVN) of hypothalamus. Lesion of neurons in the PVN with kainic acid abolished the capsaicin-induced ERR. These findings indicate that chemical stimulation of kidney causes an excitatory reflex, leading to sympathetic activation, pressor response, and accelerated heart rate. The PVN is an important central nucleus in the pathway of the ERR.

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

“…Capsaicin stimulates afferents and increases the afferent nerve activity at a low concentration, but causes denervation at a high concentration (Fitzgerald, 1983). The concentration of capsaicin in the present study was used to stimulate the renal afferents and cause ERR (Qiu et al, 2020;Ye et al, 2020;Zheng et al, 2020), which was much lower than the concentration used for denervation in previous studies (Fitzgerald, 1983;Foss et al, 2015). The capsaicin-induced ERR existed in the 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.…”

“…Our previous study has shown that the infusion of capsaicin into the cortico-medullary border of the kidney caused greater ERR effects than those in the cortex or medulla of the kidney. Infusion of capsaicin into the upper, lateral, or lower parts of the kidney showed similar ERR effects (Ye et al, 2020). Therefore, the cortico-medullary border of the lateral part of the kidney was selected for the infusion site in inducing ERR (Qiu et al, 2020;Zheng et al, 2020).…”

“…Selective removal of renal afferent fibers reduces the blood pressure and sympathetic activity in a rat model of renovascular hypertension ( Lopes et al, 2020 ). Recently, 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 capsaicin-induced ERR is mediated by angiotensin II in the hypothalamic paraventricular nucleus (PVN), which acts on AT 1 R, and in turn activates NADPH oxidase, causing oxidative stress and the subsequent NFκB activation and IL-1β production in the PVN in normal rats ( Qiu et al, 2020 ; Zheng et al, 2020 ).…”

“…The capsaicin-induced ERR is mediated by angiotensin II in the hypothalamic paraventricular nucleus (PVN), which acts on AT 1 R, and in turn activates NADPH oxidase, causing oxidative stress and the subsequent NFκB activation and IL-1β production in the PVN in normal rats ( Qiu et al, 2020 ; Zheng 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 ).…”

Neurogenic substance P—influences on action potential production in afferent neurons of the kidney?

“…Our findings in this paper and previous publications [14,49,51] as well as those of other authors [28,29] argue for a sympatho-inhibitory effect of renal afferents under normal conditions and a loss of sympatho-inhibition in pathological situations. However, we are well aware that there are also reports [50,59,62] suggesting sympatho-excitatory influences of afferent renal nerves. Probably, we must assume that both populations exist, without being able to say so far exactly when which population exerts which influence on central nervous sympathetic production under which stimulation conditions.…”