title: Non-steroidal anti-inflammatory drugs attenuate the vascular responses in aging metabolic syndrome rats.
abstract: OBJECTIVE
  Metabolic syndrome (MS) and aging are low-grade systemic inflammatory conditions, and inflammation is a key component of endothelial dysfunction. The aim of this study was to investigate the effects of non-steroidal anti-inflammatory drugs (NSAIDs) upon the vascular reactivity in aging MS rats.
  
  
  METHODS
  MS was induced in young male rats by adding 30% sucrose in drinking water over 6, 12, and 18 months. When the treatment was finished, the blood samples were collected, and aortas were dissected out. The expression of COX isoenzymes and PLA2 in the aortas was analyzed using Western blot analysis. The contractile responses of aortic rings to norepinephrine (1 μmol/L) were measured in the presence or absence of different NSAIDs (10 μmol/L for each).
  
  
  RESULTS
  Serum levels of pro-inflammatory cytokines (IL-6, TNF-α, and IL-1β) in control rats were remained stable during the aging process, whereas serum IL-6 in MS rats were significantly increased at 12 and 18 months. The levels of COX isoenzyme and PLA2 in aortas from control rats increased with the aging, whereas those in aortas from MS rats were irregularly increased with the highest levels at 6 months. Pretreatment with acetylsalicylic acid (a COX-1 preferential inhibitor), indomethacin (a non-selective COX inhibitor) or meloxicam (a COX-2 preferential inhibitor) decreased NE-induced contractions of aortic rings from MS rats at all the ages, with meloxicam being the most potent. Acetylsalicylic acid also significantly reduced the maximum responses of ACh-induced vasorelaxation of aortic rings from MS rats, but indomethacin and meloxicam had no effect.
  
  
  CONCLUSIONS
  NSAIDs can directly affect vascular responses in aging MS rats. Understanding the effects of NSAIDs on blood vessels may improve the treatment of cardiovascular diseases and MS in the elders.
authors.affiliation: Departments of Physiology, Instituto Nacional de Cardiología "Ignacio Chávez", Mexico City, Mexico.
authors.forename: María Esther
authors.initials: ME
authors.lastname: Rubio-Ruiz
authors.affiliation: Departments of Pathology, Instituto Nacional de Cardiología "Ignacio Chávez", Mexico City, Mexico.
authors.forename: Israel
authors.initials: I
authors.lastname: Pérez-Torres
authors.affiliation: Department of Reproductive Biology Instituto Nacional de Ciencias Médicas y de la Nutrición "Salvador Zubirán", Mexico City, Mexico.
authors.forename: Eulises
authors.initials: E
authors.lastname: Diaz-Diaz
authors.affiliation: Departments of Pharmacology, Instituto Nacional de Cardiología "Ignacio Chávez", Mexico City, Mexico.
authors.forename: Natalia
authors.initials: N
authors.lastname: Pavón
authors.affiliation: Departments of Physiology, Instituto Nacional de Cardiología "Ignacio Chávez", Mexico City, Mexico.
authors.forename: Verónica
authors.initials: V
authors.lastname: Guarner-Lans
mesh_terms: D000367:Age Factors; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018836:Inflammation Mediators / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D024821:Metabolic Syndrome / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D054467:Phospholipases A2 / Q000378:metabolism; D017208:Rats, Wistar; D013395:Sucrose; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; C000594089:IL1B protein, rat; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D013395:Sucrose; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496513:Ptgs1 protein, rat; C489691:Ptgs2 protein, rat; D054467:Phospholipases A2