Sawmiller D R, Linden J, Berne R M
Department of Molecular Physiology and Biological Physics, University of Virginia Health Science Center, Charlottesville 22908.
Cardiovasc Res. 1994 May;28(5):604-9. doi: 10.1093/cvr/28.5.604.
The aim was to define the contributions of interstitial and vascular adenosine in regulating coronary vascular resistance during hypoxia. To help in the assessment of adenosine in the vasodilator response, a potent adenosine receptor antagonist, xanthine amine congener (XAC), was used to block adenosine receptors.
Seven isolated guinea pig hearts were perfused at constant flow with Krebs buffer. Coronary vascular resistance was determined during normoxia (95% O2) and mild hypoxia (60% O2) in the absence or presence of 200 or 400 nM XAC. Interstitial fluid was sampled by the epicardial disc technique and the interstitial concentration of XAC (ISF[XAC]) was determined directly by a radioreceptor assay or as tritiated XAC. Venous and epicardial concentrations of adenosine were determined by high performance liquid chromatography. In six additional experiments, the vasodilator effect of 1 microM intracoronary adenosine was measured in the absence or presence of 100 or 200 nM XAC.
Mild hypoxia decreased coronary resistance by 37 (SEM 4)% in the absence of XAC and 26(5)% or 17(4)% in the presence of 200 or 400 nM XAC, respectively. ISF[XAC] rapidly equilibrated with [XAC] in the arterial perfusate or venous effluent. XAC 400 nM markedly increased (p < 0.05) the hypoxic levels of venous and epicardial fluid adenosine from 49(19) and 251(42) nM to 75(11) and 495(48) nM, respectively. XAC 100-200 nM almost completely prevented the vasodilatation induced by 1 microM intracoronary adenosine.
Adenosine mediates at least 54% of hypoxic vasodilatation. XAC rapidly equilibrates within the myocardial interstitial space and, as a result of blocking adenosine receptors, increases interstitial and venous adenosine concentrations. Increases in interstitial adenosine may partially overcome the adenosine receptor blockade by XAC, thereby reducing the effectiveness of XAC in attenuating the hypoxic vasodilatation. XAC attenuates intracoronary adenosine induced vasodilatation (mediated by endothelial adenosine receptors) much more effectively than it attenuates hypoxic vasodilatation, underscoring the minimal role played by the endothelial receptors in hypoxic vasodilatation.
旨在确定缺氧期间间质和血管腺苷在调节冠状动脉血管阻力中的作用。为了有助于评估腺苷在血管舒张反应中的作用，使用一种强效腺苷受体拮抗剂黄嘌呤胺同类物（XAC）来阻断腺苷受体。
用Krebs缓冲液以恒定流量灌注7个离体豚鼠心脏。在常氧（95% O₂）和轻度缺氧（60% O₂）条件下，在不存在或存在200或400 nM XAC的情况下测定冠状动脉血管阻力。通过心外膜圆盘技术采集间质液，并通过放射受体测定法或作为氚标记的XAC直接测定间质中XAC的浓度（ISF[XAC]）。通过高效液相色谱法测定腺苷的静脉和心外膜浓度。在另外6个实验中，在不存在或存在100或200 nM XAC的情况下，测量1 μM冠状动脉内腺苷的血管舒张作用。
在不存在XAC的情况下，轻度缺氧使冠状动脉阻力降低37（标准误4）%，在存在200或400 nM XAC的情况下，分别降低26（5）%或17（4）%。ISF[XAC]与动脉灌注液或静脉流出液中的[XAC]迅速达到平衡。400 nM的XAC使静脉和心外膜液中腺苷的缺氧水平显著升高（p < 0.05），分别从49（19）和251（42）nM升高到75（11）和495（48）nM。100 - 200 nM的XAC几乎完全阻止了1 μM冠状动脉内腺苷诱导的血管舒张。
腺苷介导至少54%的缺氧性血管舒张。XAC在心肌间质空间内迅速达到平衡，并且由于阻断腺苷受体，增加了间质和静脉中的腺苷浓度。间质腺苷的增加可能部分克服XAC对腺苷受体的阻断，从而降低XAC减弱缺氧性血管舒张的有效性。XAC减弱冠状动脉内腺苷诱导的血管舒张（由内皮腺苷受体介导）比减弱缺氧性血管舒张更有效，这突出了内皮受体在缺氧性血管舒张中所起的最小作用。
