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

• Published in: Hypertension research Vol. 35; no. 2; pp. 132 - 141
• Main Authors: Kumagai, Hiroo, Oshima, Naoki, Matsuura, Tomokazu, Iigaya, Kamon, Imai, Masaki, Onimaru, Hiroshi, Sakata, Katsufumi, Osaka, Motohisa, Onami, Toshiko, Takimoto, Chie, Kamayachi, Tadashi, Itoh, Hiroshi, Saruta, Takao
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.02.2012
• Subjects: Angiotensin II - pharmacology; Angiotensin II Type 1 Receptor Blockers - pharmacology; Animals; Blood Pressure - drug effects; Blood Pressure - physiology; Chromosomes, Human, Pair 1 - genetics; congenic rat; Electrophysiological Phenomena; Genetic Loci; Humans; Hypertension - physiopathology; Hypertension - therapy; Kidney - innervation; Kidney - physiology; Linear Models; Medulla Oblongata - cytology; Medulla Oblongata - drug effects; Medulla Oblongata - physiology; Neurons - drug effects; Neurons - physiology; Neurons, Efferent - drug effects; Neurons, Efferent - physiology; Nonlinear Dynamics; optical imaging; patch-clamp technique; Rats; Rats, Inbred SHR; Review Series; RVLM neurons; Sodium - physiology; Spinal Cord - cytology; Spinal Cord - drug effects; Spinal Cord - physiology; sympathetic nervous system; Sympathetic Nervous System - drug effects; Sympathetic Nervous System - physiology; Synapses - physiology
• DOI: 10.1038/hr.2011.208
• ISSN: 0916-9636; 1348-4214

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.