Laher I, Germann P, Dowd A L, Bevan J A
Department of Pharmacology, University of Vermont, Burlington 05405.
J Cereb Blood Flow Metab. 1989 Dec;9(6):759-64. doi: 10.1038/jcbfm.1989.109.
A number of studies indicate that relative to the maximal tone possible, for example, to histamine, noradrenaline produces only weak contractile responses in the rabbit basilar artery. Various factors, including a limited number of alpha-adrenoceptors, have been proposed to account for the reduced response to noradrenaline. We examined the effect of the Ca2+-channel activator, Bay K 8644 (0.1 and 1.0 nM) on dose-response curves to noradrenaline, histamine, calcium (Ca2+) and potassium (K+) in ring preparations of rabbit basilar artery and central ear artery. These concentrations of Bay K 8644 (0.1 and 1.0 nM) increased the magnitude of tension developed by noradrenaline (contractility) in the basilar artery, but did not alter its sensitivity (ED50) to the adrenergic vasoconstrictor. Bay K 8644 (0.1 and 1.0 nM) did not alter the contractility or sensitivity to histamine or K+ of the rabbit basilar artery. When dose-response curves to Ca2+ were made in K+-depolarized rabbit basilar artery rings, Bay K 8644 (0.1 and 1.0 nM) dose-dependently augmented tone generated by readmission of Ca2+. Bay K 8644 (0.1 and 1.0 nM) did not alter responses to noradrenaline, histamine, or K+ in rabbit central ear artery preparations. These results are compatible with a voltage-dependent mechanism of action of Bay K 8644 in the rabbit basilar artery, which may be partially depolarized in the resting state. We propose that in addition to other factors, the contractile response of rabbit basilar arteries is limited by a weak or inefficient coupling of alpha-adrenoceptors to Ca2+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)
多项研究表明，例如相对于组胺所能产生的最大张力而言，去甲肾上腺素在兔基底动脉中仅产生微弱的收缩反应。已提出包括α - 肾上腺素能受体数量有限在内的各种因素来解释对去甲肾上腺素反应减弱的原因。我们研究了Ca2 +通道激活剂Bay K 8644（0.1和1.0 nM）对兔基底动脉和中耳动脉环制剂中去甲肾上腺素、组胺、钙（Ca2 +）和钾（K +）剂量反应曲线的影响。这些浓度的Bay K 8644（0.1和1.0 nM）增加了基底动脉中去甲肾上腺素产生的张力幅度（收缩性），但未改变其对肾上腺素能血管收缩剂的敏感性（ED50）。Bay K 8644（0.1和1.0 nM）未改变兔基底动脉对组胺或K +的收缩性或敏感性。当在K +去极化的兔基底动脉环中绘制Ca2 +的剂量反应曲线时，Bay K 8644（0.1和1.0 nM）剂量依赖性地增强了重新加入Ca2 +所产生的张力。Bay K 8644（0.1和1.0 nM）未改变兔中耳动脉制剂中对去甲肾上腺素、组胺或K +的反应。这些结果与Bay K 8644在兔基底动脉中依赖电压的作用机制相符，该机制在静息状态下可能部分去极化。我们提出，除其他因素外，兔基底动脉的收缩反应受到α - 肾上腺素能受体与Ca2 +通道之间弱或低效偶联的限制。（摘要截断于250字）
