Busse R, Pohl U, Mülsch A, Bassenge E
Department of Applied Physiology, University of Freiburg, F.R.G.
J Cardiovasc Pharmacol. 1989;14 Suppl 11:S81-5. doi: 10.1097/00005344-198906152-00015.
We studied the influence of endothelium-derived relaxing factor (EDRF) on sydnonimine (SIN-1)-induced vasodilatation and the accumulation of cyclic GMP in the rabbit femoral artery. The potency of SIN-1 to elicit vasodilatation in norepinephrine-contracted femoral arteries was significantly enhanced in the absence of the endothelium or following impairment of the synthesis of EDRF with gossypol or NG-nitro-L-arginine, whether the application of SIN-1 was intra- or extraluminal. The increase in cyclic GMP in the femoral segments by a combination of SIN-1 and endothelium-derived relaxant factor (released by the endothelium of either the rabbit thoracic aorta or the femoral artery) was significantly less than the sum of the increases in cyclic GMP induced by each agent alone. In contrast, stimulation of purified soluble guanylate cyclase by submaximal concentrations of SIN-1 was additive with the effect of EDRF, released from acetylcholine-stimulated rabbit aortas. This indicates the absence of a direct interaction between the factor and SIN-1 at the level of soluble guanylate cyclase. The interaction seems to be specific for cyclic GMP-mediated responses, since cyclic AMP-induced dilatations elicited by isoproterenol were not affected by the presence of the endothelium. The results indicate that the endothelium can modulate the vascular reactivity to SIN-1. This modulation may be mediated either by EDRF or by another endothelial substance that alters the metabolism or the action of cyclic GMP in vascular smooth muscle.
我们研究了内皮源性舒张因子（EDRF）对硝普钠（SIN-1）诱导的兔股动脉血管舒张及环鸟苷酸（cGMP）蓄积的影响。无论SIN-1是腔内给药还是腔外给药，在无内皮或用棉酚或NG-硝基-L-精氨酸损害EDRF合成后，SIN-1在去甲肾上腺素预收缩的股动脉中引起血管舒张的效能均显著增强。SIN-1与内皮源性舒张因子（由兔胸主动脉或股动脉内皮释放）联合作用使股动脉段cGMP增加的幅度明显小于各药物单独作用时cGMP增加幅度之和。相反，亚最大浓度的SIN-1对纯化的可溶性鸟苷酸环化酶的刺激作用与乙酰胆碱刺激的兔主动脉释放的EDRF的作用呈相加关系。这表明在可溶性鸟苷酸环化酶水平上，该因子与SIN-1之间不存在直接相互作用。这种相互作用似乎对cGMP介导的反应具有特异性，因为异丙肾上腺素引起的环磷酸腺苷（cAMP）诱导的血管舒张不受内皮存在与否的影响。结果表明，内皮可调节血管对SIN-1的反应性。这种调节可能由EDRF介导，也可能由另一种内皮物质介导，该物质可改变血管平滑肌中cGMP的代谢或作用。
