Liard J F
Department of Physiology, Medical College of Wisconsin, Milwaukee 53226.
Am J Physiol. 1994 Jan;266(1 Pt 2):H99-106. doi: 10.1152/ajpheart.1994.266.1.H99.
Experiments were performed in conscious chronically instrumented dogs to study the mechanism of hemodynamic effects mediated by selective vasopressin V2 agonists. In one group of dogs (n = 5) instrumented for the measurement of arterial pressure and cardiac output (electromagnetic flowmeter), the infusion of NG-nitro-L-arginine methyl ester (L-NAME; 20 or 40 micrograms.kg-1 x min-1) prevented or significantly inhibited the increase in cardiac output, heart rate and systemic conductance induced by injections of 1-desamino-8-D-arginine vasopressin (DDAVP, desmopressin) and 4-valine-8-D-arginine vasopressin (VDAVP), two selective V2 agonists. L-NAME infusion did not modify the aortic adenosine 3',5'-cyclic monophosphate increase induced by DDAVP infusion. In a second group of dogs similarly prepared (n = 4), the administration of L-arginine (10 mg.kg-1 x min-1) at the same time as that of L-NAME (20 micrograms.kg-1 x min-1) completely prevented the hemodynamic effects of L-NAME and restored the response to DDAVP administration. In a third group of dogs (n = 4), the infusion of a bradykinin B2 antagonist, at a rate that significantly inhibited the cardiac output, heart rate, and blood pressure responses to bradykinin, did not modify the hemodynamic response to DDAVP infusion. We conclude that the hemodynamic effects of selective V2 agonists in dogs are not mediated by bradykinin release but instead via a V2-like receptor on endothelial cells that triggers the release of nitric oxide.
在清醒的、长期植入仪器的犬类身上进行实验,以研究选择性血管加压素V2激动剂介导的血流动力学效应机制。在一组用于测量动脉压和心输出量(电磁流量计)的犬类(n = 5)中,输注NG-硝基-L-精氨酸甲酯(L-NAME;20或40微克·千克-1·分钟-1)可预防或显著抑制注射两种选择性V2激动剂1-去氨基-8-D-精氨酸血管加压素(DDAVP,去氨加压素)和4-缬氨酸-8-D-精氨酸血管加压素(VDAVP)所诱导的心输出量、心率和全身电导增加。输注L-NAME并未改变DDAVP输注所诱导的主动脉3',5'-环磷酸腺苷增加。在另一组同样制备的犬类(n = 4)中,与L-NAME(20微克·千克-1·分钟-1)同时给予L-精氨酸(10毫克·千克-1·分钟-1)可完全预防L-NAME的血流动力学效应,并恢复对DDAVP给药的反应。在第三组犬类(n = 4)中,以显著抑制对缓激肽的心输出量、心率和血压反应的速率输注缓激肽B2拮抗剂,并未改变对DDAVP输注的血流动力学反应。我们得出结论,犬类中选择性V2激动剂的血流动力学效应不是由缓激肽释放介导的,而是通过内皮细胞上类似V2的受体触发一氧化氮释放来介导的。