title: Inhibition of Ras-GTPase improves diabetes-induced abnormal vascular reactivity in the rat perfused mesenteric vascular bed.
abstract: OBJECTIVE
  The signalling mechanisms involved in regulating altered vascular reactivity in diabetes are not fully understood. The aim of this study was to investigate the role of Ras-GTPase in the development of abnormal vascular reactivity in diabetes.
  
  
  METHODS
  We investigated the ability of chronic administration of FPTIII (1.5 mg/kg), an inhibitor of Ras-GTPase, to modulate the altered vasoreactivity of the rat perfused mesenteric bed to common vasoconstrictors and vasodilators in streptozotocin (STZ)-induced diabetes.
  
  
  RESULTS
  The vasoconstrictor responses induced by norepinephrine (NE) and endothelin-1 (ET-1) were significantly increased whereas vasodilator responses to carbachol, histamine and isoprenaline were significantly reduced in the perfused mesenteric bed of the STZ-diabetic rats. Inhibition of Ras-GTPase by chronic administration of FPTIII produced a significant normalization of the altered agonist-induced vasoconstrictor and vasodilator responses without affecting blood glucose levels. Inhibition of Ras-GTPase did not affect the agonist-induced vasoconstrictor and vasodilator responses in the control animals.
  
  
  CONCLUSIONS
  These data suggest that signal transduction pathways activated by Ras-GTPase are involved in the development of diabetic vascular dysfunction. Potential strategies aimed at modifying actions of signal transduction pathways involving Ras-GTPase may therefore prove to be beneficial in treatment of vascular complications in diabetes.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, Kuwait. mariam@hsc.kuniv.edu.kw
authors.forename: Mariam H M
authors.initials: MH
authors.lastname: Yousif
authors.forename: Ibrahim F
authors.initials: IF
authors.lastname: Benter
authors.forename: Saju
authors.initials: S
authors.lastname: Abraham
authors.forename: Saghir
authors.initials: S
authors.lastname: Akhtar
mesh_terms: D000818:Animals; D002217:Carbachol / Q000008:administration & dosage; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D019332:Endothelin-1 / Q000494:pharmacology; D005260:Female; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006632:Histamine / Q000008:administration & dosage; D006801:Humans; D007545:Isoproterenol / Q000008:administration & dosage; D008638:Mesenteric Arteries / Q000201:enzymology / Q000502:physiology*; D009638:Norepinephrine / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D018631:ras Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D019332:Endothelin-1; D006632:Histamine; D002217:Carbachol; D020558:GTP Phosphohydrolases; D018631:ras Proteins; D007545:Isoproterenol; D009638:Norepinephrine