In vitro effect of cyclosporine-A on angiotensins secretion by glomerular cells

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Abstract

Aim

Cyclosporine-A (CyA) is used to control transplant rejections and to treat autoimmune diseases. We investigated the possibility that changes induced by CyA on endothelin 1 (ET), angiotensin I (AI) and angiotensin II (AII) concentrations recognize a common pathway through which different mechanisms operate.

Methods

We measured ET, AI and AII concentrations, before and after either ET or CyA addition to the incubation medium of glomeruli of pig kidneys, isolated in vitro. The measurements were carried out with or without selective (ETA and ETB) or unselective ETA-ETB receptor inhibitors.

Results

In the presence of CyA, AI and ET are positively correlated either when ETB receptors are blocked, or when both receptors are free, while this correlation becomes negative when ETA receptors alone are blocked. Adding ET to the medium, the correlations between AI and ET are negative when either ETA, or ETB or both are blocked. The effects of CyA and ET are significant only during the first 2 h of incubation.

Conclusion

Cyclosporine-A recruits angiotensins and ET through ETA receptors, a mechanism possibly responsible of glomerular damage. This stimulation is time-dependent. Prevention of the renal damage from CyA should require selective ETA receptor blockade.

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