Modification of arterial smooth muscle reactivity in cyclosporine A pretreated arteries

Abstract

Background In the present study the interactions between phenylephrine - selective α₁-adrenoceptor agonist, arg-vasopressine - selective agonist of vasopressine receptor type 1 (V₁) and modulator - cyclosporine A were investigated.
Material and methods Experiments were performed on perfused rat tail arteries. Using classical pharmacometric methods the relationship between concentration-response curves (CRCs) for agonists performed in the absence and presence of cyclosporine A were analyzed.
Results In the presence of cyclosporine A the reduction in ED₅₀ values for agonists was observed. Dissociation constants for agonists calculated in the presence of cyclosporine A did not differ significantly from controls.
Conclusions Changes in plots of agonists responses against receptor occupancy for agonists and changes in K_A/ED₅₀ value suggest increase in receptor reserve. This increase was not significantly reduced in the presence of losartan. Our results suggest that changes in receptor reserve are result of changes in signal transduction.