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(Hypertension. 2009;53:42.)
© 2009 American Heart Association, Inc.

Original Articles

Relation of Blood Pressure Quantitative Trait Locus on Rat Chromosome 1 to Hyperactivity of Rostralventrolateral Medulla

Kamon Iigaya; Hiroo Kumagai; Toru Nabika; Yuji Harada; Hiroshi Onimaru; Naoki Oshima; Chie Takimoto; Tadashi Kamayachi; Takao Saruta; Hiroshi Itoh

From the Division of Endocrinology, Metabolism, and Nephrology (K.I., N.O., C.T., T.K., T.S., H.I.), Department of Internal Medicine, Keio University School of Medicine, Tokyo; Department of Nephrology (H.K.), National Defense Medical College, Tokorozawa, Saitama; Department of Pathology (T.N., Y.H.), Shimane University School of Medicine, Izumo; and Department of Physiology (H.O.), Showa University School of Medicine, Tokyo, Japan.

Correspondence to Kamon Iigaya, Discipline of Physiology, F13, University of Sydney, New South Wales 2006, Australia. E-mail kamon{at}physiol.usyd.edu.au

Genetic factors that induce essential hypertension have been examined using genome-wide linkage analyses. A quantitative trait locus (QTL) region that is closely linked to hypertension has been found on chromosome 1 in stroke-prone spontaneously hypertensive rats (SHRSPs). We used 2 congenic rats in which the blood pressure QTL on rat chromosome 1 was introgressed from SHRSP/Izm to Wistar-Kyoto (WKY)/Izm (WKYpch1.0) and from WKY/Izm to SHRSP/Izm (SHRSPwch1.0) rats by repeated backcrossing. Previous studies reported that the intermediate phenotype of this QTL for hypertension is characterized by the hyperactivity of the sympathetic nervous system in response to physiological and psychological stress. We performed intracellular patch-clamp recordings of rostral ventrolateral medulla (RVLM) neurons from WKY, WKYpch1.0, SHRSPwch1.0, and SHRSPs and compared the basal electrophysiological activities of RVLM neurons and the responses of these neurons to angiotensin II. The basal membrane potential of RVLM neurons from WKYpch1.0 was significantly "shallower" than that of the neurons from WKY. The depolarization of RVLM neurons from WKYpch1.0 in response to angiotensin II was significantly larger than that in neurons from WKY rats, whereas the depolarization of RVLM neurons from SHRSPwch1.0 was significantly smaller than that in neurons from SHRSPs. The response to angiotensin II of RVLM neurons from WKYpch1.0 and SHRSPs was sustained even after the blockade of all of the synaptic transmissions using tetrodotoxin. The QTL on rat chromosome 1 was primarily related to the postsynaptic response of RVLM bulbospinal neurons to brain angiotensin II, whereas both the QTL and other genomic regions influenced the basal activity of RVLM neurons.

Key Words: sympathetic nervous system • congenic rat • angiotensin II • stress • RVLM neurons

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