Carrier M, Tronc F, Stewart D, Nattel S, Pelletier L C
Department of Cardiovascular Surgery, Montreal Heart Institute, Quebec, Canada.
J Thorac Cardiovasc Surg. 1993 Sep;106(3):487-90.
The calcium channel blocker diltiazem has been shown to reduce cyclosporine toxicity both in clinical and in experimental studies. To determine the effect of diltiazem administration on cyclosporine vasoconstriction and on renal release of endothelin, we administered cyclosporine in models of renal and hind limb autoperfusion in the dog. Infusion of cyclosporine in the hind limb (20 mg) during diltiazem perfusion caused an average increase of 6 +/- 2 mm Hg in hind limb perfusion pressure compared with 17 +/- 2 mm Hg before diltiazem, a significant difference (p < 0.05). Similarly, injections of cyclosporine (10 mg) in the kidney during diltiazem infusion caused an average increase of 26 +/- 4 mm Hg in renal perfusion pressure compared with 83 +/- 13 mm Hg before diltiazem infusion, a significant decrease in the renal vascular response (p < 0.05). On the other hand, sodium nitroprusside did not change the renal vasoconstriction to cyclosporine, which suggests a specific effect of diltiazem. Serum levels of endothelin in renal venous blood increased from 0.5 +/- 0.4 pg/ml to 3.8 +/- 0.6 pg/ml with cyclosporine, despite diltiazem infusion. Therefore, although the calcium channel blocker diltiazem effectively decreases cyclosporine-induced renal and hind limb vasoconstriction, it does not act by preventing endothelin release induced by cyclosporine stimulation.
钙通道阻滞剂地尔硫䓬已在临床和实验研究中显示可降低环孢素毒性。为确定给予地尔硫䓬对环孢素引起的血管收缩及肾内皮素释放的影响，我们在犬的肾和后肢自身灌注模型中给予环孢素。在灌注地尔硫䓬期间，后肢输注环孢素（20毫克）使后肢灌注压平均升高6±2毫米汞柱，而在给予地尔硫䓬前为17±2毫米汞柱，差异有统计学意义（p<0.05）。同样，在输注地尔硫䓬期间，肾内注射环孢素（10毫克）使肾灌注压平均升高26±4毫米汞柱，而在输注地尔硫䓬前为83±13毫米汞柱，肾血管反应显著降低（p<0.05）。另一方面，硝普钠未改变环孢素引起的肾血管收缩，这提示地尔硫䓬有特异性作用。尽管输注了地尔硫䓬，但环孢素仍使肾静脉血中内皮素血清水平从0.5±0.4皮克/毫升升至3.8±0.6皮克/毫升。因此，尽管钙通道阻滞剂地尔硫䓬可有效降低环孢素引起的肾和后肢血管收缩，但其作用并非通过阻止环孢素刺激诱导的内皮素释放来实现。
