Lack of beneficial metabolic effects of quercetin in adult spontaneously hypertensive rats.

Abstract

Insulin sensitivity is partly dependent on insulin-mediated nitric oxide (NO) release and antioxidants may decrease insulin resistance by amelioring NO bioavailability. The effects of chronic therapy with the antioxidant quercetin on blood pressure, vascular function and glucose tolerance in male spontaneously hypertensive rats (SHR), a model of genetically hypertension and insulin resistance, were analyzed. Rats were divided into four groups, WKY vehicle, WKY quercetin, SHR vehicle and SHR quercetin. Animals were daily administered by gavage for four weeks: vehicle, quercetin in vehicle (10mg/kg body weight). Blood pressure was followed by tail-cuff plethysmography. Chronic quercetin treatment reduced systolic blood pressure, and significantly reduced left ventricular (-10%) and renal (-6%) hypertrophy. However, oral glucose tolerance test, homeostatic model assessment of insulin resistance, total cholesterol and triglycerides were unaffected by quercetin in both strains of rats. It also improved the blunted aortic endothelium-dependent relaxation to acetylcholine, without affecting both endothelium-dependent relaxation to insulin and endothelium-independent relaxation to sodium nitroprusside in SHR. In WKY rats, quercetin in vitro and in vivo, impaired the relaxation to insulin. Quercetin reduced both plasma malondialdehyde levels and aortic superoxide production in SHR. Furthermore, quercetin inhibited insulin-stimulated protein kinase B (Akt)- and endothelial NO synthase (eNOS) phosphorylation. In conclusion, quercetin reduced blood pressure, left ventricular and renal hypertrophy and improved NO-dependent acetylcholine relaxation. However, and despite its antioxidant effects, quercetin was unable to improve insulin sensitivity possibly through its specific interference with the insulin signalling pathway.

• Authors: Miguel Romero, Rosario Jiménez, Belén Hurtado, Juan Manuel Moreno, Isabel Rodríguez-Gómez, Rocío López-Sepúlveda, Antonio Zarzuelo, Francisco Pérez-Vizcaino, Juan Tamargo, Félix Vargas, Juan Duarte
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 627 Issue 1-3 Pg. 242-50 (Feb 10 2010) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 19903466 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2009 Elsevier B.V. All rights reserved.

Chemical References

• Insulin
• Quercetin
• Nitric Oxide Synthase Type III
• Proto-Oncogene Proteins c-akt
• Glucose

Topics

• Administration, Oral
• Animals
• Aorta (drug effects, metabolism)
• Cell Line
• Fasting
• Glucose (administration & dosage, pharmacology)
• Homeostasis (drug effects)
• Humans
• Hypertension (complications, drug therapy, metabolism, physiopathology)
• In Vitro Techniques
• Insulin (metabolism, pharmacology)
• Insulin Resistance
• Male
• Nitric Oxide Synthase Type III (metabolism)
• Oxidation-Reduction
• Phosphorylation (drug effects)
• Proto-Oncogene Proteins c-akt (metabolism)
• Quercetin (administration & dosage, pharmacology, therapeutic use)
• Rats
• Rats, Inbred SHR
• Signal Transduction (drug effects)