Vascular endothelial dysfunction in cyclosporine-treated rat aortas is not associated with serum total homocysteine levels.
OBJECTIVE
Elevation of serum total homocysteine (tHcy) is considered to contribute to endothelial cell dysfunction, which is considered to be the initial event in posttransplant vascular disease. We sought to investigate whether an association existed between serum tHcy levels and vascular endothelial function during cyclosporine (CsA) treatment.


METHODS
Endothelium-dependent and -independent relaxation responses (to acetylcholine [ACh] and sodium nitroprusside [SNP]) were determined on thoracic aortae from CsA-treated rats (5 mg kg/d, subcutaneously, for 14 days). A correlation analysis was performed between ACh responses and tHcy levels.


RESULTS
CsA decreased the responses to ACh and the pD(2) values of the concentration-response curves compared with controls (P < .05). Responses to SNP and serum tHcy levels were unchanged among the groups. tHcy negatively correlated with the ACh pD(2) values among control (r = -0.69; P < .05) and vehicle (r = -0.73; P < .05) groups, indicating that the increase in tHcy was associated with decreased sensitivity to ACh. In CsA-treated rats, no association was observed between these parameters. Also, no correlation was noted between CsA concentrations and tHcy levels.


CONCLUSIONS
These data suggested a possible link between serum tHcy and decreased vascular sensitivity to endothelium-dependent vasorelaxation in control aortae, but CsA-induced vascular endothelial dysfunction was not associated with an effect of the drug on homocysteine metabolism.
Can
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C
Department of Pharmacology, Ege University School of Medicine, Bornova, Izmir, Turkey.
Erol
A
A
Olukman
M
M
Cinar
M G
MG
Ulker
S
S
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology*; D016572:Cyclosporine / Q000097:blood / Q000494:pharmacology*; D004655:Emulsions / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D006710:Homocysteine / Q000097:blood*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D004655:Emulsions; D007166:Immunosuppressive Agents; D006710:Homocysteine; D009599:Nitroprusside; C022131:cremophor; D011092:Polyethylene Glycols; D016572:Cyclosporine