Abraham J S, Bentley F R, Garrison R N
Department of Surgery, University of Louisville School of Medicine, Louisville 40292.
J Invest Surg. 1993 Sep-Oct;6(5):401-12. doi: 10.3109/08941939309141627.
Calcium channel blockade has been found to attenuate nephrotoxicity of cyclosporine. However, it is not known whether intrarenal vasoconstriction caused by cyclosporine is totally mediated by vascular smooth muscle calcium influx. To study the protective effects of two calcium blockers on cyclosporine-induced intrarenal vasoconstriction and renal microvascular blood flow, hydronephrotic rat kidneys were suspended in an environmentally controlled tissue bath. Renal microvessel diameters and microvascular blood flow were determined by in vivo videomicroscopy and Doppler velocimetry. Calcium channel blockade was achieved by adding verapamil hydrochloride (5.6 x 10(-5) M) or diltiazem hydrochloride (2.8 x 10(-5) M) to the tissue bath, which respectively resulted in a 15 +/- 2% and 16 +/- 3% interlobular arteriolar dilation, a 13 +/- 3% and 12 +/- 2% afferent arteriolar dilation, and a 60 +/- 8% and 46 +/- 14% increase in interlobular blood flow. When cyclosporine (1.7 x 10(-3) M) was added to the tissue bath, there was a constriction of the interlobular arterioles to 4 +/- 3% below baseline in rats receiving verapamil and 9 +/- 3% below baseline in rats receiving diltiazem. Microvascular blood flow was reduced by the addition of cyclosporine to 3 +/- 4% above original baseline values in the verapamil group and 22 +/- 6% below baseline in the diltiazem group. Afferent arterioles were similarly constricted by cyclosporine. The results indicate that calcium blockade causes preglomerular vasodilation and protects the microvascular blood flow induced by cyclosporine. Since verapamil or diltiazem did not prevent arteriolar constriction as observed when cyclosporine was added, it was concluded that the mechanism of acute cyclosporine-induced vasoconstriction is not solely mediated by vascular smooth muscle calcium influx through potential dependent channels.
已发现钙通道阻滞剂可减轻环孢素的肾毒性。然而，尚不清楚环孢素引起的肾内血管收缩是否完全由血管平滑肌钙内流介导。为研究两种钙阻滞剂对环孢素诱导的肾内血管收缩和肾微血管血流的保护作用，将肾积水大鼠的肾脏置于环境可控的组织浴中。通过体内视频显微镜和多普勒测速法测定肾微血管直径和微血管血流。通过向组织浴中加入盐酸维拉帕米（5.6×10⁻⁵ M）或盐酸地尔硫䓬（2.8×10⁻⁵ M）实现钙通道阻滞，这分别导致小叶间动脉扩张15±2%和16±3%，入球小动脉扩张13±3%和12±2%，小叶间血流增加60±8%和46±14%。当向组织浴中加入环孢素（1.7×10⁻³ M）时，接受维拉帕米的大鼠小叶间动脉收缩至基线以下4±3%，接受地尔硫䓬的大鼠小叶间动脉收缩至基线以下9±3%。加入环孢素后，维拉帕米组微血管血流减少至高于原始基线值3±4%，地尔硫䓬组微血管血流减少至基线以下22±6%。入球小动脉也受到环孢素类似的收缩作用。结果表明，钙阻滞可引起肾小球前血管舒张，并保护环孢素诱导的微血管血流。由于加入环孢素时观察到维拉帕米或地尔硫䓬并不能防止小动脉收缩，因此得出结论，急性环孢素诱导的血管收缩机制并非完全由通过电压依赖性通道的血管平滑肌钙内流介导。
