Lodge N J, Zhang R, Halaka N N, Moreland S
Department of Pharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000, USA.
Eur J Pharmacol. 1995 Dec 20;287(3):279-85. doi: 10.1016/0014-2999(95)00494-7.
The functional importance of endothelin ETA and ETB receptors in selected arterial and venous smooth muscle preparations was characterized. Endothelin-1 induced force in the saphenous and jugular veins is normally mediated by endothelin ETB-like receptors. However, desensitization or pharmacological block of these receptors reveals an endothelin ETA receptor population that is of sufficient size to mediate full endothelin-1-evoked force. Block of either endothelin ETA or endothelin ETB receptors alone is insufficient to antagonize endothelin-1-evoked force in saphenous vein. Endothelin-1-induced force in hamster aorta may also be mediated by activation of both endothelin ETA and ETB receptors. However, activation of endothelin ETB-like receptors alone is insufficient to generate a full endothelin-1 response. Sarafotoxin S6c treatment, to desensitize endothelin ETB receptors, failed to affect the responses of rat aorta and rabbit carotid artery to endothelin-1 or endothelin ETA receptor antagonists. These findings indicate that selective endothelin receptor antagonists will vary enormously in their efficacy against endothelin-induced force in different vascular beds.
研究了内皮素ETA和ETB受体在特定动脉和静脉平滑肌制剂中的功能重要性。内皮素-1在隐静脉和颈静脉中诱导的张力通常由类内皮素ETB受体介导。然而，这些受体的脱敏或药理学阻断揭示了一个内皮素ETA受体群体，其大小足以介导内皮素-1诱发的全部张力。单独阻断内皮素ETA或内皮素ETB受体不足以拮抗隐静脉中内皮素-1诱发的张力。内皮素-1在仓鼠主动脉中诱导的张力也可能由内皮素ETA和ETB受体的激活共同介导。然而，仅激活类内皮素ETB受体不足以产生完整的内皮素-1反应。用沙拉毒素S6c处理以使内皮素ETB受体脱敏，未能影响大鼠主动脉和兔颈动脉对内皮素-1或内皮素ETA受体拮抗剂的反应。这些发现表明，选择性内皮素受体拮抗剂在不同血管床中对抗内皮素诱发张力的功效差异极大。
