Effect of p22phox depletion on sympathetic regulation of blood pressure in SHRSP: evaluation in a new congenic strain.
Oxidative stress in the rostral ventrolateral medulla (RVLM), a sympathetic center in the brainstem, was implicated in the regulation of sympathetic activity in various hypertensive models including stroke-prone spontaneously hypertensive rats (SHRSP). In this study, we evaluated the role of the NADPH oxidases (NOX) in the blood pressure (BP) regulation in RVLM in SHRSP. The P22PHOX-depleted congenic SHRSP (called SP.MES) was constructed by introducing the mutated p22phox gene of Matsumoto Eosinophilic Shinshu rat. BP response to glutamate (Glu) microinjection into RVLM was compared among SHRSP, SP.MES, SHR and Wistar Kyoto (WKY); the response to Glu microinjection was significantly greater in SHRSP than in SP.MES, SHR and WKY. In addition, tempol, losartan and apocynin microinjection reduced the response to Glu significantly only in SHRSP. The level of oxidative stress, measured in the brainstem using lucigenin and dihydroethidium, was reduced in SP.MES than in SHRSP. BP response to cold stress measured by telemetry system was also blunted in SP.MES when compared with SHRSP. The results suggested that oxidative stress due to the NOX activation in RVLM potentiated BP response to Glu in SHRSP, which might contribute to the exaggerated response to stress in this strain.
Department of Functional Pathology, Shimane University School of Medicine, Izumo, Japan.
Hasan M
HM
Zahid
Department of Functional Pathology, Shimane University School of Medicine, Izumo, Japan.
Mohammed Zubaerul
MZ
Ferdaus
Department of Functional Pathology, Shimane University School of Medicine, Izumo, Japan.
Hiroki
H
Ohara
Department of Functional Pathology, Shimane University School of Medicine, Izumo, Japan.
Minoru
M
Isomura
Department of Functional Pathology, Shimane University School of Medicine, Izumo, Japan.
Toru
T
Nabika
D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D020296:Animals, Congenic; D000975:Antioxidants / Q000737:chemistry; D001794:Blood Pressure / Q000187:drug effects; D001933:Brain Stem / Q000187:drug effects; D003080:Cold Temperature; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004996:Ethidium / Q000031:analogs & derivatives / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D019255:NADPH Oxidases / Q000235:genetics / Q000502:physiology*; D018384:Oxidative Stress; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017382:Reactive Oxygen Species / Q000737:chemistry; D013113:Spin Labels; D020521:Stroke / Q000235:genetics / Q000503:physiopathology*; D013481:Superoxides / Q000737:chemistry*; D013564:Sympathetic Nervous System / Q000187:drug effects
D000098:Acetophenones; D000975:Antioxidants; D003497:Cyclic N-Oxides; D017382:Reactive Oxygen Species; D013113:Spin Labels; C067883:dihydroethidium; D013481:Superoxides; C056165:acetovanillone; D019255:NADPH Oxidases; C515768:Cyba protein, rat; D004996:Ethidium; D019808:Losartan; C001803:tempol