title: Effect of age and COX-2-derived prostanoids on the progression of adult vascular dysfunction in the offspring of diabetic rats.
abstract: OBJECTIVE
  The present study was designed to determine how diabetes in pregnancy affects vascular function in their offspring, the influence of age and whether COX activation is involved in this effect.
  
  
  METHODS
  Relaxation responses to ACh were analysed in mesenteric resistance arteries from the offspring of control rats (O-CR) and those of diabetic rats (O-DR) at 3, 6 and 12 months of age. TxB₂, PGE₂ and PGF(2α) release were determined by enzyme immunoassay. COX-1 and COX-2 expression were measured by Western blot analysis.
  
  
  RESULTS
  O-DR developed hypertension from 6 months of age compared with O-CR. In O-DR, relaxation responses to ACh were impaired in all ages studied and were restored by COX-2 inhibition. TP receptor blockade (SQ29548) restored ACh relaxation in arteries from 3-month-old O-DR while TP and EP receptor blockade (SQ29548 + AH6809) was required to restore it in 6-month-old O-DR. In 12-month-old O-DR, ACh relaxation was restored when TP, EP and FP receptors were blocked (SQ29548 + AH6809 + AL8810). ACh-stimulated TxB₂ was higher in all O-DR. ACh-stimulated PGE₂ release was increased in arteries from 6- and 12-month-old O-DR, whereas PGF(2α) was increased only in 12-month-old O-DR. COX-2, but not COX-1, expression was higher in O-DR than O-CR.
  
  
  CONCLUSIONS
  The results indicate an age-dependent up-regulation of COX-2 coupled to an enhanced formation of vasoconstrictor prostanoids in resistance arteries from O-DR. This effect plays a key role in the pathogenesis of endothelial dysfunction, which in turn could contribute to the progression of vascular dysfunction in these rats.
authors.affiliation: Departamento de Fisiologia e Farmacologia, Universidade Federal de Pernambuco, Recife, Brazil.
authors.forename: F E
authors.initials: FE
authors.lastname: Ramos-Alves
authors.forename: D B
authors.initials: DB
authors.lastname: de Queiroz
authors.forename: J
authors.initials: J
authors.lastname: Santos-Rocha
authors.forename: G P
authors.initials: GP
authors.lastname: Duarte
authors.forename: F E
authors.initials: FE
authors.lastname: Xavier
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure; D051545:Cyclooxygenase 1 / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D008638:Mesenteric Arteries / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D011247:Pregnancy; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001786:Blood Glucose; D008565:Membrane Proteins; D011453:Prostaglandins; D009599:Nitroprusside; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496513:Ptgs1 protein, rat; C489691:Ptgs2 protein, rat; D000109:Acetylcholine