This Article Full Text Full Text (PDF) All Versions of this Article: 46/2/349    most recent 01.HYP.0000173421.97463.acv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Matsuura, T. Articles by Saruta, T. Search for Related Content PubMed PubMed Citation Articles by Matsuura, T. Articles by Saruta, T. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Related Collections Autonomic, reflex, and neurohumoral control of circulation ACE/Angiotension receptors Genetically altered mice

(Hypertension. 2005;46:349.)
© 2005 American Heart Association, Inc.

Original Articles

Electrophysiological Properties of Rostral Ventrolateral Medulla Neurons in Angiotensin II 1a Receptor Knockout Mice

Tomokazu Matsuura; Hiroo Kumagai; Hiroshi Onimaru; Akira Kawai; Kamon Iigaya; Toshiko Onami; Katsufumi Sakata; Naoki Oshima; Takeshi Sugaya; Takao Saruta

From the Department of Internal Medicine (T.M., H.K., K.I., T.O., K.S., N.O., T. Saruta), Keio University School of Medicine, Tokyo, Japan; Department of Physiology (H.O., A.K.), Showa University School of Medicine, Tokyo, Japan; and Discovery Laboratory (T. Sugaya), Tanabe Seiyaku Co, Ltd, Osaka, Japan.

Correspondence to Hiroo Kumagai, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. E-mail hkumagai{at}sc.itc.keio.ac.jp

We compared the electrophysiological properties of neurons in the rostral ventrolateral medulla of neonatal angiotensin II type 1a receptor knockout mice and wild-type mice with responses to angiotensin II, its type-1 receptor blocker candesartan, and its type-2 receptor blocker PD123319. Using the whole-cell patch-clamp technique, we examined the characteristics of rostral ventrolateral medulla neurons in brain stem-spinal cord preparations in which the sympathetic neuronal network is preserved. Baseline membrane potential and firing rate were almost similar between angiotensin II type 1a receptor knockout mice and wild-type mice. Superfusion with angiotensin II depolarized rostral ventrolateral medulla bulbospinal neurons in wild-type mice, whereas it hyperpolarized those in angiotensin II type 1a receptor knockout mice. Because pretreatment with candesartan significantly prevented the angiotensin II-induced depolarization in wild-type mice, the angiotensin II type 1 receptor is crucial for this depolarization. Superfusion with PD123319 depolarized rostral ventrolateral medulla bulbospinal neurons in angiotensin II type 1a receptor knockout mice. PD123319 prevented the angiotensin II-induced hyperpolarization in angiotensin II type 1a receptor knockout mice, and, rather, it induced depolarization. These results suggest that the angiotensin II type 2 receptor in rostral ventrolateral medulla plays an antagonistic role against the angiotensin II type 1a receptor in controlling the neuronal activity of rostral ventrolateral medulla.

Key Words: angiotensin antagonist • angiotensin II • brain • central nervous system • mice • receptors, angiotensin II • sympathetic nervous system

This article has been cited by other articles:

				L. Gao, W. Wang, W. Wang, H. Li, C. Sumners, and I. H. Zucker Effects of Angiotensin Type 2 Receptor Overexpression in the Rostral Ventrolateral Medulla on Blood Pressure and Urine Excretion in Normal Rats Hypertension, February 1, 2008; 51(2): 521 - 527. [Abstract] [Full Text] [PDF]

				K. Iigaya, H. Kumagai, H. Onimaru, A. Kawai, N. Oshima, T. Onami, C. Takimoto, T. Kamayachi, K. Hayashi, T. Saruta, et al. Novel axonal projection from the caudal end of the ventrolateral medulla to the intermediolateral cell column Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2007; 292(2): R927 - R936. [Abstract] [Full Text] [PDF]