Hypertension after cardiac transplantation: pathophysiology and management
作者:
Mikael Sander,
Ronald Victor,
期刊:
Current Opinion in Nephrology and Hypertension
(OVID Available online 1995)
卷期:
Volume 4,
issue 5
页码: 443-451
ISSN:1062-4821
年代: 1995
出版商: OVID
数据来源: OVID
摘要:
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 FK5O6. 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.
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