Thromboxane-dependent coronary vasoconstriction in obese mice: Role of peroxynitrite

• Published in: Prostaglandins & other lipid mediators Vol. 160; p. 106631
• Main Authors: Villa-Martínez, Elisa, López-Vaquera, Selma Romina, Alvarado-Coutiño, Lesvia Karina, Gámez-Méndez, Ana María, Ríos, Amelia, Escalante, Bruno
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2022
• Subjects: Animals; Arachidonic acid; Arachidonic Acid - metabolism; Cyclooxygenase 2; Endothelial dysfunction; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Obesity - metabolism; Peroxynitrite; Peroxynitrous Acid - pharmacology; Thromboxane A2; Thromboxanes; Vasoconstriction; Endothelial dysfunction; Obesity; Peroxynitrite; Arachidonic acid; Thromboxane A2
• ISSN: 1098-8823
• DOI: 10.1016/j.prostaglandins.2022.106631

Obesity leads to chronic oxidative stress promoting the development of cardiovascular diseases including coronary artery disease and endothelial dysfunction. Increased reactive oxygen species production associated with obesity might lead to endothelial dysfunction through cyclooxygenase (COX) pathway. We evaluated arachidonic acid (AA)-dependent coronary vascular responses and explored COX metabolism in obese C57BL/6 mice. In response to arachidonic acid (AA), isolated hearts from obese mice showed increased vasoconstriction compared with control mice. Released thromboxane (TX) A2 during AA-induced vasoconstriction phase was increased in heart perfusates from obese mice. Indomethacin and 1-benzylimidazole, both reduced vasoconstriction response in control and obese mice. Vasoconstriction response to TXA2 mimetic analog U46619 was 2.7 higher in obese mice. Obesity increased COX-2, TXS and TX receptor protein expression as well as oxidative stress evaluated by nitrotyrosine and peroxynitrite levels, compared with control mice. Obese mice treated with FeTMPyP, a peroxynitrite scavenger, reversed all these parameters to control levels. These data suggest that alterations in COX pathway may be associated with increased generation of free radicals, including peroxynitrite, that result from the oxidative stress observed in obesity. •Obesity is associated with chronic oxidative stress.•Increased reactive oxygen species in obesity leads to coronary artery disease and endothelial dysfunction.•Augmented cyclooxygenase and thromboxane synthase protein expression in obese mice induced vasoconstriction.•Thromboxane A2-dependent vasoconstriction is mediated by increased generation of peroxynitrite.•The vasoconstriction response to thromboxane A2 mimetic analog U46619 was increased in obese mice.