Importance of rostral ventrolateral medulla neurons in determining efferent sympathetic nerve activity and blood pressure

Abstract

Accentuated sympathetic nerve activity (SNA) is a risk factor for cardiovascular events. In this review, we investigate our working hypothesis that potentiated activity of neurons in the rostral ventrolateral medulla (RVLM) is the primary cause of experimental and essential hypertension. Over the past decade, we have examined how RVLM neurons regulate peripheral SNA, how the sympathetic and renin-angiotensin systems are correlated and how the sympathetic system can be suppressed to prevent cardiovascular events in patients. Based on results of whole-cell patch-clamp studies, we report that angiotensin II (Ang II) potentiated the activity of RVLM neurons, a sympathetic nervous center, whereas Ang II receptor blocker (ARB) reduced RVLM activities. Our optical imaging demonstrated that a longitudinal rostrocaudal column, including the RVLM and the caudal end of ventrolateral medulla, acts as a sympathetic center. By organizing and analyzing these data, we hope to develop therapies for reducing SNA in our patients. Recently, 2-year depressor effects were obtained by a single procedure of renal nerve ablation in patients with essential hypertension. The ablation injured not only the efferent renal sympathetic nerves but also the afferent renal nerves and led to reduced activities of the hypothalamus, RVLM neurons and efferent systemic sympathetic nerves. These clinical results stress the importance of the RVLM neurons in blood pressure regulation. We expect renal nerve ablation to be an effective treatment for congestive heart failure and chronic kidney disease, such as diabetic nephropathy.

Central GPR109A Activation Mediates Glutamate-Dependent Pressor Response in Conscious Rats

“…Here we present the first evidence that GPR109A is expressed in RVLM neurons, including the TH-expressing neurons (Fig. 2, A and B); the latter modulate the sympathetic activity and BP (Guyenet, 2006;Kumagai et al, 2012). These findings, which infer a cardiovascular role for GPR109A, were confirmed by observing dose-related increases in BP after intra-RVLM NA microinjection in conscious rats (Fig.…”

“…The objective of this experiment was to determine whether GPR109A is expressed in the RVLM and in PC12 cells and its spatial distribution in the RVLM relative to different cell types, particularly tyrosine hydroxylase (TH) immunoreactive (ir) neurons, which modulate the sympathetic activity and BP (Guyenet, 2006;Kumagai et al, 2012). First, Western blot (WB) analysis was conducted to detect GPR109A in PC12 cell lysate and in punches taken from the RVLM of naïve rats (n 5 3).…”

Selective Proximal Renal Denervation Guided by Autonomic Responses Evoked via High-Frequency Stimulation in a Preclinical Canine Model

“…18 Renal afferent reflex could activate rostral ventrolateral medulla neurons in the brain, alter systemic sympathetic nervous activity, and contribute to the development of hypertension. 19 Accordingly, it was hypothesized that destroying either efferent or afferent renal nerves could result in hypotensive effect of RDN. In the present study, radiofrequency energy application was guided by previous evoked BP rises with HFS within the lumen of the renal arteries.…”

Blood Pressure and Autonomic Responses to Electrical Stimulation of the Renal Arterial Nerves Before and After Ablation of the Renal Artery

“…Stimulation of the afferent sympathetic nerve increases systemic sympathetic nerve activity and causes vasoconstriction via the activation of rostral ventrolateral medulla neurons in the brain. [16][17][18][19] Accordingly, the attenuation of either the efferent or afferent sympathetic renal nerve theoretically contributes to lower the systemic BP. Indeed, experimental renal denervation, performed to clarify the role of these nerves in increasing the BP, decreased the BP in several models of hypertension.…”