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Hypertension after cardiac transplantation: pathophysiology and management
1Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA.
Current Opinion in Nephrology and Hypertension
|September 1, 1995
Summary
Cyclosporine A causes hypertension after heart transplants by inhibiting calcineurin, a mechanism shared with FK506 but not rapamycin. This highlights calcineurin as a key target for managing drug-induced side effects.
Area of Science:
- Nephrology
- Immunology
- Cardiology
Background:
- Cyclosporine A is a vital immunosuppressant post-heart transplant.
- Hypertension is a significant side effect of cyclosporine A therapy.
- The molecular mechanisms underlying cyclosporine A's dual actions require elucidation.
Purpose of the Study:
- To review the pathophysiology and management of cyclosporine A-induced hypertension.
- To explore the hypothesis that calcineurin inhibition mediates both immunosuppressive and hypertensive effects of cyclosporine A.
- To compare the toxicity profiles of cyclosporine A, FK506, and rapamycin.
Main Methods:
- Literature review of current knowledge on cyclosporine A-induced hypertension.
- Examination of experimental evidence at the whole animal and cellular levels.
- Analysis of data from multicenter clinical trials.
Main Results:
- Calcineurin is identified as the common cellular target for cyclosporine A and FK506.
- Cyclosporine A and FK506 share similar toxicity profiles, including hypertension.
- Rapamycin, which does not affect calcineurin, shows a different toxicity profile.
Conclusions:
- Calcineurin inhibition is hypothesized to mediate cyclosporine A-induced hypertension and toxicity.
- FK506 mimics cyclosporine A's hypertensive and toxic effects, supporting the calcineurin hypothesis.
- Further research is needed to understand rapamycin's clinical toxicity.