In vitro effect of cyclosporine-A on angiotensins secretion by glomerular cells.
OBJECTIVE
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 (ET(A) and ET(B)) or unselective ET(A)-ET(B) receptor inhibitors.


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


CONCLUSIONS
Cyclosporine-A recruits angiotensins and ET through ET(A) receptors, a mechanism possibly responsible of glomerular damage. This stimulation is time-dependent. Prevention of the renal damage from CyA should require selective ET(A) receptor blockade.
Bergamasco
Luca
L
Department of Clinical and Experimental Medicine, Eastern Piedmont University, Novara, Italy.
Sainaghi
Pier Paolo
PP
Castello
Luigi
L
Letizia
Claudio
C
Bartoli
Ettore
E
D000803:Angiotensin I / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D016572:Cyclosporine / Q000633:toxicity*; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism; D005260:Female; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D044022:Receptor, Endothelin A / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000378:metabolism; D013552:Swine; D013997:Time Factors; D046509:Tissue Culture Techniques; D015854:Up-Regulation
D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D007166:Immunosuppressive Agents; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D000804:Angiotensin II; C082887:PD 145065; C086539:BQ 788; D016572:Cyclosporine; D000803:Angiotensin I; C072247:cyclo(Trp-Asp-Pro-Val-Leu)