Vascular endothelial dysfunction in cyclosporine-treated rat aortas is not associated with serum total homocysteine levels.

Abstract

OBJECTIVES:

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.

MATERIALS AND 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.

CONCLUSION:

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.

• Authors: C Can, A Erol, M Olukman, M G Cinar, S Ulker
• Journal: Transplantation proceedings (Transplant Proc) Vol. 40 Issue 10 Pg. 3702-6 (Dec 2008) ISSN: 0041-1345 [Print] United States
• PMID: 19100469 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Emulsions
• Immunosuppressive Agents
• Homocysteine
• Nitroprusside
• cremophor
• Polyethylene Glycols
• Cyclosporine

Topics

• Animals
• Aorta, Thoracic (drug effects, physiology)
• Cyclosporine (blood, pharmacology)
• Emulsions (pharmacology)
• Endothelium, Vascular (drug effects, physiopathology)
• Homocysteine (blood)
• Immunosuppressive Agents (pharmacology)
• In Vitro Techniques
• Male
• Nitroprusside (pharmacology)
• Polyethylene Glycols (pharmacology)
• Rats
• Rats, Wistar
• Vasoconstriction (drug effects)
• Vasodilation (drug effects)