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

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Abstract

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.

Original languageEnglish
Pages (from-to)42-48
Number of pages7
JournalHypertension
Volume53
Issue number1
DOIs
Publication statusPublished - 2009 Jan

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Chromosomes, Human, Pair 1
Quantitative Trait Loci
Blood Pressure
Neurons
Angiotensin II
Hypertension
Physiological Stress
Inbreeding
Inbred WKY Rats
Sympathetic Nervous System
Tetrodotoxin
Inbred SHR Rats
Psychological Stress
Synaptic Transmission
Membrane Potentials
Stroke
Genome

Keywords

  • Angiotensin II
  • Congenic rat
  • RVLM neurons
  • Stress
  • Sympathetic nervous system

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Relation of blood pressure quantitative trait locus on rat chromosome 1 to hyperactivity of rostralventrolateral medulla. / Iigaya, Kamon; Kumagai, Hiroo; Nabika, Toru; Harada, Yuji; Onimaru, Hiroshi; Oshima, Naoki; Takimoto, Chie; Kamayachi, Tadashi; Saruta, Takao; Itoh, Hiroshi.

In: Hypertension, Vol. 53, No. 1, 01.2009, p. 42-48.

Research output: Contribution to journalArticle

Iigaya, K, Kumagai, H, Nabika, T, Harada, Y, Onimaru, H, Oshima, N, Takimoto, C, Kamayachi, T, Saruta, T & Itoh, H 2009, 'Relation of blood pressure quantitative trait locus on rat chromosome 1 to hyperactivity of rostralventrolateral medulla', Hypertension, vol. 53, no. 1, pp. 42-48. https://doi.org/10.1161/HYPERTENSIONAHA.108.117804
Iigaya, Kamon ; Kumagai, Hiroo ; Nabika, Toru ; Harada, Yuji ; Onimaru, Hiroshi ; Oshima, Naoki ; Takimoto, Chie ; Kamayachi, Tadashi ; Saruta, Takao ; Itoh, Hiroshi. / Relation of blood pressure quantitative trait locus on rat chromosome 1 to hyperactivity of rostralventrolateral medulla. In: Hypertension. 2009 ; Vol. 53, No. 1. pp. 42-48.
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