RRC ID 4350
Author Iigaya K, Kumagai H, Nabika T, Harada Y, Onimaru H, Oshima N, Takimoto C, Kamayachi T, Saruta T, Itoh H.
Title Relation of blood pressure quantitative trait locus on rat chromosome 1 to hyperactivity of rostral ventrolateral medulla.
Journal Hypertension
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.
Volume 53(1)
Pages 42-8
Published 2009-1-1
DOI 10.1161/HYPERTENSIONAHA.108.117804
PMID 19047583
MeSH Angiotensin II / pharmacology Animals Animals, Congenic Blood Pressure / genetics* Blood Pressure / physiology* Chromosomes / genetics* Electrophysiological Phenomena Hypertension / genetics* Hypertension / physiopathology* Hypothalamus / physiopathology Medulla Oblongata / physiopathology* Membrane Potentials / drug effects Membrane Potentials / physiology Neurons / drug effects Neurons / physiology Patch-Clamp Techniques Quantitative Trait Loci / genetics* Rats Rats, Inbred SHR Rats, Inbred WKY Sodium Channel Blockers / pharmacology Tetrodotoxin / pharmacology Vasoconstrictor Agents / pharmacology
IF 7.713
Times Cited 10
Rats WKY.SHRSP-(D1Wox29-D1Arb21)/Izm(strainID=318) SHRSP.WKY-(D1Wox29-D1Arb21)/Izm(strainID=480)