Abstract 11564: Oral Administration of Telmisartan Causes Sympathoinhibition through the Blockade of AT1 Receptor in the Cardiovascular Center of Brainstem and the Activation of the Systemic PPAR-γ in Metabolic Syndrome
Backgrounds: Activation of the sympathetic nervous system (SNS) is involved in the pathogenesis of metabolic syndrome (MetS). We have demonstrated that angiotensin II type 1 receptor (AT1R)-induced oxidative stress in the rostral ventrolateral medulla (RVLM) of the brainstem activates the SNS. Telmisartan, an AT1R blocker (ARB) and partial agonist for peroxisome proliferator-activated receptor gamma (PPARγ), is approved for the treatment of MetS with hypertension. The aim of this study was to determine whether oral administration of telmisartan decreases the activity of the SNS through the blockade of AT1R in the RVLM and activation of systemic PPAR-γ in MetS.
Methods and Results: Male Sprague-Dawley rats were fed on a high-fat diet and segregated into obesity-prone (OP) showed a MetS profile and obesity-resistant (OR) after 13 weeks. OP was divided into OP treated with the pral administration of telmisartan (TLM-OP), OP treated with the oral administration of telmisartan and GW9662, PPARγ antagonist, (TLM+GW-OP) and vehicle (VEH-OP). Urinary norepinephrine excretion (uNE), as a marker of the activity of the SNS, was significantly lower in TLM-OP than in VEH-OP (1.2±0.2 ug vs 1.9±0.2 ug, n=5, p<0.01), and the reduction of uNE was attenuated in TLM+GW-OP (1.5±0.1 ug/day, n=5). Presser effects due to the microinjection of angiotensin II into the RVLM was significantly smaller in TLM-OP than in VEH-OP (8±4mmHg vs 21±5mmHg, n=5 for each, p<0.01), and was significantly greater in TLM+GW-OP than in TLM-OP (15±3mmHg vs. 8±4mmHg, n=5 for each, p<0.01).
Conclusion: In MetS, oral administration of telmisartan suppresses SNS through the blockade of AT1R in the RVLM and activation of systemic PPARγ. Since telmisartan has powerful sympathoinhibitory effects, it would be a reasonable choice in treating patients with MetS.
- © 2011 by American Heart Association, Inc.