OBJECTIVES: 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. METHODS AND 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. CONCLUSION: 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.
OBJECTIVES: 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 hypertensiverats. 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. METHODS AND RESULTS:Obesity-prone rats fed a high-fat diet were divided into groups treated with either telmisartanobesity-prone (TLM-OP), or losartanobesity-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. CONCLUSION: 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.