title: In vitro effects of the organophosphorus pesticide malathion on the reactivity of rat aorta.
abstract: OBJECTIVE
  There is a remarkable paucity of studies analyzing the role of the endothelium-derived relaxing factors on the vascular effects of organophosphates. This study was carried out to evaluate the vascular effects of malathion and the role of nitric oxide (NO) and prostacyclin (PGI2).
  
  
  METHODS
  Vascular reactivity measuring isometric forces in vitro ('organ chambers') and flow cytometry (cells loaded with DAF-FM DA) were used.
  
  
  RESULTS
  In rat thoracic aorta segments contracted with phenylephrine (Phe) (10(-7) mol/l), malathion (10(-10) to 10(-5) mol/l) induced concentration-dependent relaxation in arteries with intact endothelium (n = 7; p < 0.05). Malathion-mediated relaxation was blocked by N-nitro-L-arginine methyl ester (L-NAME; 10(-4) mol/l), a nonspecific NO synthase inhibitor, and/or indomethacin (10(-5) mol/l), a nonspecific cyclooxygenase inhibitor (n = 10, p < 0.05). In thoracic aorta rings, with and without endothelium, Phe (10(-10) to 10(-5) mol/l) evoked concentration-dependent contraction, which was reduced in the presence of malathion. In rings with or without endothelium, incubated with malathion, L-NAME and indomethacin, the Phe-induced contraction was restored. The role of NO was confirmed using flow cytometry. Malathion evokes endothelium-dependent relaxation through the M1 muscarinic receptor, since this relaxation was clearly blocked by atropine (M1 and M2 blocker) and pirenzepine (M1 blocker), but was less blocked by gallamine (M2 blocker) or 4-DAMP (M3 blocker).
  
  
  CONCLUSIONS
  These findings suggest that the organophosphate compound effects on vascular reactivity depend of NO and PGI2.
authors.affiliation: Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: Marco Tulio Menezes
authors.initials: MT
authors.lastname: de Carvalho
authors.forename: Andrea Carla
authors.initials: AC
authors.lastname: Celotto
authors.forename: Agnes Afrodite Sumarelli
authors.initials: AA
authors.lastname: Albuquerque
authors.forename: Luciana Garros
authors.initials: LG
authors.lastname: Ferreira
authors.forename: Verena Kise
authors.initials: VK
authors.lastname: Capellini
authors.forename: Ana Paula Cassiano
authors.initials: AP
authors.lastname: Silveira
authors.forename: Tales Rubens
authors.initials: TR
authors.lastname: de Nadai
authors.forename: Paulo Roberto Barbosa
authors.initials: PR
authors.lastname: Evora
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D001285:Atropine / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D011464:Epoprostenol / Q000502:physiology; D005703:Gallamine Triethiodide / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008294:Malathion / Q000494:pharmacology*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010575:Pesticides / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D018727:Muscarinic Antagonists; D010575:Pesticides; D010880:Piperidines; D014665:Vasodilator Agents; D010656:Phenylephrine; D009569:Nitric Oxide; D010890:Pirenzepine; D001285:Atropine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D011464:Epoprostenol; D019001:Nitric Oxide Synthase; D005703:Gallamine Triethiodide; D008294:Malathion; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin