钙拮抗剂在无内皮的情况下可抑制大鼠主动脉对去甲肾上腺素的收缩反应，但在内皮存在时则无此作用。

Calcium antagonists inhibit contractions to norepinephrine in the rat aorta, in the absence, but not in the presence of the endothelium.

Auch-Schwelk W, Vanhoutte P M

Baylor College of Medicine, Houston, TX 77030.

Gen Pharmacol. 1991;22(4):595-602. doi: 10.1016/0306-3623(91)90062-b.

Abstract

To compare the effect of diltiazem and verapamil on the responsiveness of vascular smooth muscle to norepinephrine in the presence and absence of the endothelium, rings of rat aorta were studied in organ chambers. 2. The removal of the endothelium decreased the ED50 to norepinephrine and augmented the maximal response to the catecholamine. 3. The contraction to norepinephrine consisted of a rapid initial (phasic) and a (tonic) part. The tonic part was reduced in the presence of the endothelium. 4. Diltiazem shifted the concentration-response curve to norepinephrine to the right only in rings without endothelium and reduced the difference in maximal response between rings with and without endothelium. 5. Verapamil abolished the difference in sensitivity (ED50) between rings with and without endothelium. 6. Oxyhemoglobin prevented the inhibitory effect of the endothelium on the response to norepinephrine, and unmasked a shift of the ED50 to the catecholamine to the right by diltiazem in rings with endothelium. 7. These experiments suggest that spontaneously released endothelium-derived relaxing factor(s) is a functional antagonist of norepinephrine-induced contractions, presumably by reducing the stimulated influx of extracellular Ca2+.

摘要

为了比较地尔硫䓬和维拉帕米在有内皮和无内皮情况下对血管平滑肌对去甲肾上腺素反应性的影响，在器官浴槽中研究了大鼠主动脉环。2. 去除内皮降低了对去甲肾上腺素的半数有效剂量（ED50），并增强了对儿茶酚胺的最大反应。3. 对去甲肾上腺素的收缩由快速初始（相性）和（紧张性）部分组成。在有内皮的情况下，紧张性部分降低。4. 地尔硫䓬仅在无内皮的环中将去甲肾上腺素的浓度-反应曲线向右移动，并减少了有内皮和无内皮环之间最大反应的差异。5. 维拉帕米消除了有内皮和无内皮环之间敏感性（ED50）的差异。6. 氧合血红蛋白阻止了内皮对去甲肾上腺素反应的抑制作用，并揭示了地尔硫䓬在有内皮的环中使对儿茶酚胺的ED50向右移动。7. 这些实验表明，自发释放的内皮源性舒张因子可能通过减少细胞外Ca2+的刺激内流，是去甲肾上腺素诱导收缩的功能性拮抗剂。