Sympathoinhibitory effects of telmisartan through the reduction of oxidative stress in the rostral ventrolateral medulla of obesity-induced hypertensive rats.
OBJECTIVE
Sympathetic nervous system (SNS) activity is critically involved in the development and progression of obesity-induced hypertension. Angiotensin II type 1 receptor (AT1R)-induced oxidative stress in the rostral ventrolateral medulla (RVLM), a vasomotor center in the brainstem, activates the SNS in hypertensive rats. The aim of the present study was to determine whether oral administration of an AT1R blocker (ARB) inhibits SNS activity via antioxidative effects in the RVLM of rats with dietary-induced obesity.


RESULTS
Obesity-prone rats fed a high-fat diet were divided into groups treated with either telmisartan obesity-prone (TLM-OP), or losartan obesity-prone (LOS-OP), or vehicle obesity-prone (VEH-OP). SBP, SNS activity, and oxidative stress in the RVLM were significantly higher in obesity-prone rats than in obesity-resistant rats. Body weight, visceral fat, blood glucose, serum insulin, and plasma adiponectin concentrations were significantly lower in TLM-OP and LOS-OP than in VEH-OP, and plasma adiponectin concentrations were significantly higher in TLM-OP than in LOS-OP. Although SBP was reduced to similar levels both in TLM-OP and LOS-OP, both oxidative stress in the RVLM and SNS activity were significantly lower in TLM-OP than in LOS-OP or VEH-OP.


CONCLUSIONS
Orally administered telmisartan inhibited SNS activity through antioxidative effects via AT1R blockade in the RVLM of obesity-prone rats. AT1R and oxidative stress in the RVLM might be novel treatment targets for obesity-induced hypertension through sympathoinhibition, and telmisartan might be preferable for obesity-induced hypertension.
Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Satomi
S
Konno
Yoshitaka
Y
Hirooka
Takuya
T
Kishi
Kenji
K
Sunagawa
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D001794:Blood Pressure; D001933:Brain Stem / Q000187:drug effects* / Q000378:metabolism; D006339:Heart Rate; D006973:Hypertension / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008845:Microinjections; D009638:Norepinephrine / Q000652:urine; D009765:Obesity / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077333:Telmisartan; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001565:Benzoates; D017392:Thiobarbituric Acid Reactive Substances; D000077333:Telmisartan; D009638:Norepinephrine