Decreased endothelium-dependent vasodilation in diabetic female rats: role of prostanoids.
Overproduction of vasoconstrictor prostanoids and reduced prostacyclin levels have been related to the male diabetic-linked vascular dysfunction. However, it is not clear yet if these changes also occur in diabetic females. The aim of this study was to verify the role of prostanoids in the vascular dysfunction of diabetic female rats. The parameters studied were the mesenteric arteriolar reactivity (intravital microscopy and isolated perfused arteriolar bed), prostanoid measurement (enzyme immunoassay), superoxide generation (intravital fluorescence microscopy), and the presence of peroxynitrite (Western blot for nitrotyrosine-containing proteins). The response to acetylcholine was decreased in arterioles of diabetic female rats and diclofenac, but not ridogrel, corrected the altered response. The unstimulated (basal) release of thromboxane B2 (TXB2), but not prostaglandin F2alpha (PGF2alpha) or 6-keto-PGF1alpha, was increased in the mesenteric perfusate from diabetic female rats. Increased production of PGF2alpha and 6-keto-PGF1alpha, but not TXB2, was induced by acetylcholine in diabetic arterioles. The superoxide generation was increased in diabetic female rats and diclofenac corrected it. Diabetes increased nitrotyrosine-containing proteins in mesenteric microvessels. In conclusion, our data show that the increase of constrictor prostanoid release, most likely PGF2alpha, could be involved in the reduced endothelium-dependent vasodilation of diabetic female rats. In addition, the enhanced activation of cyclooxygenase may be a source of superoxide anion generation in this model.
Akamine
Eliana H
EH
Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Urakawa
Tiyeko Anna Eliza V M
TA
de Oliveira
Maria Aparecida
MA
Nigro
Dorothy
D
de Carvalho
Maria Helena C
MH
de Cássia A Tostes
Rita
R
Fortes
Zuleica B
ZB
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000503:physiopathology; D001920:Bradykinin / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D006632:Histamine / Q000494:pharmacology; D008638:Mesenteric Arteries / Q000503:physiopathology; D009569:Nitric Oxide / Q000502:physiology*; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D013481:Superoxides; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D006632:Histamine; D000109:Acetylcholine; D001920:Bradykinin