van den Ende R, Batink H D, Pfaffendorf M, van Zwieten P A
Division of Pharmacotherapy, Academic Medical Center, University of Amsterdam, The Netherlands.
J Cardiovasc Pharmacol. 1991 Nov;18(5):679-86. doi: 10.1097/00005344-199111000-00005.
The influence of global ischemia on cardiac beta-adrenoceptors was studied in rat and guinea pig Langendorff hearts (LH), both by functional and binding experiments using the specific beta-adrenoceptor ligand (-)-[125I]-iodocyanopindolol. Neither ischemia (30 or 60 min) nor postischemic reperfusion caused any change in beta-adrenoceptor density, affinity or in the beta 1/beta 2 ratio in LH of normal rats or in LH of rats pretreated with reserpine or 6-hydroxydopamine (6-OHDA), or in guinea pig LH, whereas perfusion of rat LH with 10(-5) M isoprenaline (15 min) caused the expected decrease in beta-adrenoceptor density. After ischemia, isoprenaline was no longer able to influence beta-adrenoceptor density, suggesting that the internalization mechanism is impaired. In functional studies, perfusion of the rat LH with 10(-5) M isoprenaline (15 min) shifted the concentration-response curve for isoprenaline to the right. Thirty-minute global ischemia virtually abolished the inotropic but not the chronotropic response to isoprenaline. Ischemia did not impair the inotropic response to ouabain or to calcium, indicating that the contractile apparatus itself was still largely intact. Our results suggest that the contractile failure after ischemia is not caused by a decrease in beta-adrenoceptor density or by a defect in the contractile apparatus but by an impaired second-messenger system.
利用特异性β - 肾上腺素能受体配体（-）-[¹²⁵I] - 碘氰吲哚洛尔，通过功能实验和结合实验，研究了整体缺血对大鼠和豚鼠离体灌流心脏（Langendorff心脏，LH）β - 肾上腺素能受体的影响。无论是缺血（30或60分钟）还是缺血后再灌注，正常大鼠的LH、经利血平或6 - 羟基多巴胺（6 - OHDA）预处理的大鼠的LH或豚鼠的LH，其β - 肾上腺素能受体密度、亲和力或β₁/β₂比值均未发生任何变化，而用10⁻⁵ M异丙肾上腺素灌注大鼠LH（15分钟）会导致β - 肾上腺素能受体密度如预期那样降低。缺血后，异丙肾上腺素不再能够影响β - 肾上腺素能受体密度，这表明内化机制受损。在功能研究中，用10⁻⁵ M异丙肾上腺素灌注大鼠LH（15分钟）使异丙肾上腺素的浓度 - 反应曲线右移。30分钟的整体缺血几乎消除了对异丙肾上腺素的变力作用，但未消除变时作用。缺血并未损害对哇巴因或钙的变力反应，这表明收缩装置本身在很大程度上仍然完好。我们的结果表明，缺血后的收缩功能衰竭不是由β - 肾上腺素能受体密度降低或收缩装置缺陷引起的，而是由第二信使系统受损所致。
