Hypertension after cardiac transplantation: pathophysiology and management.
Hypertension after cardiac transplantation: pathophysiology and management.
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心脏移植后高血压：病理生理学和治疗。
DOI：
10.1097/00041552-199509000-00013
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发表时间：
1995
影响因子：
3.2
通讯作者：
Victor,RG
中科院分区：
文献类型：
--
作者：
Sander,M;Victor,RG
本文综述了环孢素a引起的心脏移植术后高血压及其病理生理和治疗的最新进展。提出了一种共同的分子机制介导环孢素的免疫抑制和高血压作用。钙-钙调素依赖性磷酸酶钙调磷酸酶是介导环孢素A和FK5O6显著免疫抑制作用的常见细胞靶点。钙调磷酸酶在神经系统、肌肉和肾脏等非淋巴组织中含量更丰富。由于这些是环孢素a诱导毒性的主要靶点，最近有人假设抑制钙调磷酸酶介导环孢素a诱导的毒性。这一假设得到了越来越多的实验证据的支持，在整个动物和细胞水平上，表明环孢素A的毒性谱被FK506复制，而不是被雷帕霉素复制，雷帕霉素是FK506的结构类似物，是一种有效的免疫抑制剂，但对钙调磷酸酶没有影响。最近的多中心试验表明，在临床环境中，环孢素A的高血压和其他副作用与FK506相同。雷帕霉素的临床毒性尚不清楚。
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.