TY - JOUR
T1 - Thromboxane-dependent coronary vasoconstriction in obese mice
T2 - Role of peroxynitrite
AU - Villa-Martínez, Elisa
AU - López-Vaquera, Selma Romina
AU - Alvarado-Coutiño, Lesvia Karina
AU - Gámez-Méndez, Ana María
AU - Ríos, Amelia
AU - Escalante, Bruno
N1 - Funding Information:
This work was supported by the Mexican Council for Science and Technology (CONACyT, México, grant number 1180 to BAE). EV, SRLV, and LKAC are fellows from CONACyT, México.
Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2022/6
Y1 - 2022/6
N2 - 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.
AB - 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.
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U2 - 10.1016/j.prostaglandins.2022.106631
DO - 10.1016/j.prostaglandins.2022.106631
M3 - Article
C2 - 35272056
SN - 1098-8823
VL - 160
SP - 106631
JO - Journal of Lipid Mediators and Cell Signalling
JF - Journal of Lipid Mediators and Cell Signalling
M1 - 106631
ER -
