Kong J Q, Taylor D A, Fleming W W
Department of Pharmacology and Toxicology, West Virginia University Health Sciences Center, Morgantown.
J Pharmacol Exp Ther. 1994 Mar;268(3):1153-9.
Because alpha-1 adrenoceptor subtypes are distributed differentially in different arteries, experiments were conducted to determine the functional contribution of these subtypes in conduit vs. resistance vessels. Concentration- or dose-response curves for norepinephrine were obtained from aortic rings, superior mesenteric artery rings or the isolated perfused mesenteric vasculature from male Sprague-Dawley rats. Frequency-response curves to transmural electrical stimulation were obtained from the latter two preparations. The effects of 5-methylurapidil (5-MU), an alpha-1a adrenoceptor antagonist, and chloroethyl-clonidine (CEC), an alpha-1b adrenoceptor antagonist, on contractile responses were determined. In artery rings, 5-MU (30 nM) had no effect on the EC50 of norepinephrine but reduced the maximum response of the mesenteric artery rings by nearly 25%. In the perfused mesenteric vasculature, however, 5-MU (30 nM) shifted the ED50 for norepinephrine about 40-fold while reducing the maximum response by 30%. 5-MU depressed the frequency-response curve in the perfused mesenteric vasculature by nearly 80%, but did not alter the response of artery rings. In aorta, pretreatment with CEC (10 microM) shifted the concentration-response curve of norepinephrine by 800-fold without effecting the maximum. In mesenteric artery rings and perfused mesenteric vasculature, CEC reduced the slope and maximum response of both frequency-response and norepinephrine dose-response curves. Responses to norepinephrine (10 microM) in the perfused mesentery were abolished by 5-MU and reduced only 25% by nifedipine. These data suggest that the density or role of alpha-1a adrenoceptors may be greater in resistance vessels than in conduit vessels.
由于α-1肾上腺素能受体亚型在不同动脉中的分布存在差异，因此进行了实验以确定这些亚型在传导血管与阻力血管中的功能作用。从雄性Sprague-Dawley大鼠的主动脉环、肠系膜上动脉环或离体灌注的肠系膜血管系统中获取去甲肾上腺素的浓度-或剂量-反应曲线。从后两种制剂中获得对跨壁电刺激的频率-反应曲线。测定了α-1a肾上腺素能受体拮抗剂5-甲基尿嘧啶（5-MU）和α-1b肾上腺素能受体拮抗剂氯乙可乐定（CEC）对收缩反应的影响。在动脉环中，5-MU（30 nM）对去甲肾上腺素的EC50没有影响，但使肠系膜动脉环的最大反应降低了近25%。然而，在灌注的肠系膜血管系统中，5-MU（30 nM）使去甲肾上腺素的ED50移动了约40倍，同时使最大反应降低了30%。5-MU使灌注的肠系膜血管系统中的频率-反应曲线降低了近80%，但没有改变动脉环的反应。在主动脉中，用CEC（10 μM）预处理使去甲肾上腺素的浓度-反应曲线移动了800倍，而不影响最大值。在肠系膜动脉环和灌注的肠系膜血管系统中，CEC降低了频率-反应曲线和去甲肾上腺素剂量-反应曲线的斜率和最大反应。5-MU消除了灌注肠系膜中对去甲肾上腺素（10 μM）的反应，硝苯地平仅使其降低了25%。这些数据表明，α-1a肾上腺素能受体在阻力血管中的密度或作用可能比在传导血管中更大。
