Relation of blood pressure quantitative trait locus on rat chromosome 1 to hyperactivity of rostral ventrolateral medulla.
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.
Iigaya
Kamon
K
Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Tokyo. kamon@physiol.usyd.edu.au
Kumagai
Hiroo
H
Nabika
Toru
T
Harada
Yuji
Y
Onimaru
Hiroshi
H
Oshima
Naoki
N
Takimoto
Chie
C
Kamayachi
Tadashi
T
Saruta
Takao
T
Itoh
Hiroshi
H
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D020296:Animals, Congenic; D001794:Blood Pressure / Q000235:genetics* / Q000502:physiology*; D002875:Chromosomes / Q000235:genetics*; D055724:Electrophysiological Phenomena; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology*; D007031:Hypothalamus / Q000503:physiopathology; D008526:Medulla Oblongata / Q000503:physiopathology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D040641:Quantitative Trait Loci / Q000235:genetics*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D026941:Sodium Channel Blockers; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D013779:Tetrodotoxin