INDUCTION OF CONTRACTION IN ISOLATED RAT AORTA BY CYCLOSPORINE
INDUCTION OF CONTRACTION IN ISOLATED RAT AORTA BY CYCLOSPORINE
复制标题
环孢素诱导离体大鼠主动脉收缩
作者：
H. Xue;R. Bukoski;D. McCarron;W. Bennett
环孢素(CsA)是一种新型免疫抑制剂，具有肾毒性和高血压的不良反应。据推测，相反作用的机制是通过 CsA 对血管平滑肌的作用。为了检验这一假设，从 Wister京都大鼠中分离出胸主动脉，并准备用于测量张力的环段。 CsA (5 ± 10-6M) 诱导孤立环的张力缓慢增加，3 小时时的响应为 0.70 ± 0.17 N/m2 × 10-4。Ca2+ 通道阻滞剂维拉帕米（3 小时后为 0.30 ± 0.08 N/m2 × 104，P<0.05）和非竞争性α-拮抗剂显着抑制这种收缩。苯氧苯扎明（3小时后0.06±0.07N/m2×104，P<0.05）。竞争性α-拮抗剂酚妥拉明具有混合效应。 CsA 不会不可逆地改变血管平滑肌收缩能力，因为接触该药物 3 小时对最大收缩反应或对 KC1 的敏感性没有影响。我们得出结论，CsA 可以直接诱导血管平滑肌收缩，可能是通过诱导肾上腺素能神经末梢释放去甲肾上腺素。这些数据与 CsA 通过对血管平滑肌的收缩作用诱发肾毒性和新发高血压的假设是一致的。
Cyclosporine (CsA) is a new immunosuppressive agent that has adverse effects of nephrotoxicity and de novo appearance of hypertension. It has been hypothesized that the mechanism of the contrary effects is through an action of CsA on vascular smooth muscle. To test this hypothesis, thoracic aortas were isolated from Wister Kyoto rats and ring segments prepared for measurement of tension. CsA (5 ± 10-6M) induced a slow increase in tone of the isolated rings with a response at 3 hr of 0.70 ± 0.17 N/m2 × 10-4 This contraction was significantly inhibited by the Ca2+ channel blocker verapamil (0.30 ± 0.08 N/m2 × 104 after 3 hr, P<0.05) and by the noncompetitive a-antagonist phenoxybenzamine (0.06 ± 0.07 N/m2 × 104 after 3 hr, P<0.05). The competitive a-antagonist phentolamine had mixed effects. CsA does not irreversibly alter vascular smooth muscle contractile ability since a 3 hr exposure to the agent had no effect on either the maximal contractile response or sensitivity to KC1. We conclude that CsA can directly induce contraction in vascular smooth muscle, perhaps by inducing a release of norepinephrine from adrenergic nerve terminals. The data are consistent with the hypothesis that CsA induces nephrotoxicity and de novo hypertension through a contractile effect on vascular smooth muscle.