Purdy R E, Ashbrook D W, Stupecky G L, Watanabe M Y
J Pharmacol Exp Ther. 1983 Mar;224(3):543-51.
The alpha adrenoceptor properties of the rabbit ear artery and thoracic aorta were assessed using isolated blood vessel rings mounted in tissue baths. Labetalol, an alpha and beta receptor antagonist, caused dose-dependent contractions in control, reserpinized and surgically denervated ear arteries. This contraction was inhibited by phentolamine and abolished by the irreversible alpha receptor antagonist, N,N'-bis-(O-methoxy-benzylaminohexyl) cystamine tetrahydrochloride. Thoracic aorta failed to respond to labetalol. Using labetalol as an antagonist against methoxamine, labetalol pA2 values were 7.4 +/- 0.3 (95% confidence interval) and 7.13 +/- 0.25 in ear artery and aorta, respectively. Thus, labetalol had the same affinity for the alpha receptors of these two vessels but was an alpha agonist only in the ear artery. Norepinephrine ED50 values and dissociation constants (KA) were determined by analysis of dose-response data with and without partial inactivation of alpha receptors by phenoxybenzamine. Ear artery and aorta norepinephrine ED50 values, 4.24 (2.24-8.03) X 10(-8) M and 2.48(1.64-3.76) X 10(-8) M, respectively, were not significantly different. In contrast, norepinephrine KA values differed by a factor of 32, 4.11 (3.02-5.60) X 10(-6) M and 1.29 (0.85-1.94) X 10(-7) M, respectively. Receptor reserves were also markedly different in these vessels. Thus, ED50 was achieved with 1% receptor occupancy in ear artery as compared to 16% receptor occupancy in aorta. It is concluded that the alpha receptors of ear artery and aorta are both qualitatively and quantitatively different.
使用安装在组织浴槽中的离体血管环评估兔耳动脉和胸主动脉的α肾上腺素能受体特性。拉贝洛尔是一种α和β受体拮抗剂，在对照、利血平化和手术去神经的耳动脉中引起剂量依赖性收缩。这种收缩被酚妥拉明抑制，并被不可逆的α受体拮抗剂N，N'-双-(O-甲氧基苄基氨基己基)胱胺四盐酸盐消除。胸主动脉对拉贝洛尔无反应。以拉贝洛尔作为甲氧明的拮抗剂，拉贝洛尔在耳动脉和主动脉中的pA2值分别为7.4±0.3（95%置信区间）和7.13±0.25。因此，拉贝洛尔对这两种血管的α受体具有相同的亲和力，但仅在耳动脉中是α激动剂。通过分析有无苯氧苄胺对α受体的部分失活作用的剂量反应数据来确定去甲肾上腺素的ED50值和解离常数(KA)。耳动脉和主动脉的去甲肾上腺素ED50值分别为4.24(2.24 - 8.03)×10(-8)M和2.48(1.64 - 3.76)×10(-8)M，无显著差异。相比之下，去甲肾上腺素的KA值相差32倍，分别为4.11(3.02 - 5.60)×10(-6)M和1.29(0.85 - 1.94)×10(-7)M。这些血管中的受体储备也明显不同。因此，在耳动脉中1%的受体占有率即可达到ED50，而在主动脉中则需要16%的受体占有率。结论是，耳动脉和主动脉的α受体在质和量上均不同。
