Hypertension after cardiac transplantation: pathophysiology and management.
This article reviews the current state of knowledge concerning cyclosporine A-induced hypertension after heart transplantation, its pathophysiology and management. The hypothesis is presented that a common molecular mechanism mediates both the immunosuppressive and the hypertensive actions of cyclosporine. The calcium-calmodulin dependent phosphatase, calcineurin, is the common cellular target mediating the salient immunosuppressive effects of both cyclosporine A and FK506. Calcineurin is even more plentiful in nonlymphoid tissues such as the nervous system, muscle, and kidney. Because these are the main target sites for cyclosporine A-induced toxicity, it has been hypothesized recently that inhibition of calcineurin mediates cyclosporine A-induced toxicity. This hypothesis is supported by increasing experimental evidence, at both the whole animal and cellular levels, indicating that the toxicity profile of cyclosporine A is duplicated by FK506 but not by rapamycin, a structural analog of FK506 which is a potent immunosuppressive agent but has no effect on calcineurin. Recent multicenter trials demonstrate that in the clinical setting the hypertensive and other side effects of cyclosporine A are duplicated by FK506. The clinical toxicity of rapamycin is as yet unknown.
Sander
M
M
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA.
Victor
R G
RG
D000818:Animals; D016572:Cyclosporine / Q000009:adverse effects*; D016027:Heart Transplantation; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology / Q000628:therapy; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D016572:Cyclosporine