Edwards B S, Lloyd M A, Anderson L M
Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota 55905.
Transplantation. 1993 Jan;55(1):8-11. doi: 10.1097/00007890-199301000-00002.
Cyclosporine represents the foundation for current immunosuppressive therapy following solid organ transplantation. CsA use is associated with renal insufficiency and systemic hypertension. We hypothesized that CsA would enhance the vascular actions of endothelin (ET). Three groups of anesthesized dogs (n = 15) were studied. Group 1 received CsA alone (1 mg/kg), group 2 received ET alone (1 ng/kg/min), and group 3 received combined CsA (1 mg/kg) and ET (1 ng/kg/min). The hemodynamic and renal effects were evaluated after 30 min. Combined treatment resulted in a profound reduction in mean arterial pressure (-62 +/- 14 mmHg (P < .05) and cardiac output (-2.2 +/- 0.4.1/min (P < .05). The reduction in mean arterial pressure and cardiac output were significantly greater than that observed with CsA or ET alone. Systemic vascular resistance was not significantly changed. Combined CsA and ET resulted in a significant reduction in renal blood flow (195 +/- 18 to 101 +/- 11 ml/mm P < .05) but without evidence of active renal vasoconstriction. The decline in GFR (31.8 +/- 5.6 ml/min to being unmeasurable) was of greater magnitude than the change in renal blood flow, suggesting enhanced afferent anteriolar vasoconstriction or an alteration in the ultrafiltration coefficient. These studies demonstrate an important and synergistic cardiodepressor effect when CsA and ET are combined.
环孢素是目前实体器官移植后免疫抑制治疗的基础。使用环孢素与肾功能不全和系统性高血压有关。我们假设环孢素会增强内皮素（ET）的血管作用。研究了三组麻醉犬（n = 15）。第1组单独接受环孢素（1 mg/kg），第2组单独接受内皮素（1 ng/kg/min），第3组接受环孢素（1 mg/kg）和内皮素（1 ng/kg/min）联合治疗。30分钟后评估血流动力学和肾脏效应。联合治疗导致平均动脉压显著降低（-62±14 mmHg，P <.05）和心输出量显著降低（-2.2±0.4 L/min，P <.05）。平均动脉压和心输出量的降低显著大于单独使用环孢素或内皮素时观察到的降低。全身血管阻力没有显著变化。环孢素和内皮素联合使用导致肾血流量显著减少（从195±18降至101±11 ml/min，P <.05），但没有明显的肾血管主动收缩证据。肾小球滤过率的下降（从31.8±5.6 ml/min降至无法测量）幅度大于肾血流量的变化，提示入球小动脉血管收缩增强或超滤系数改变。这些研究表明，环孢素和内皮素联合使用时具有重要的协同性心脏抑制作用。
