Lee S L, Levitsky S, Feinberg H
Department of Pharmacology, University of Illinois College of Medicine, Chicago.
J Pharmacol Exp Ther. 1989 Jan;248(1):44-9.
The in situ heart is exposed to blood-borne vasoconstrictor agents (e.g., vasopressin) which, if unopposed, may cause radically increased coronary vascular resistance (CVR). Release of endogenous vasodilator, such as prostacyclin (PGI2), is a possible mitigating mechanism. We investigated the ability of the heart to maintain CVR within a narrow range when exposed to exogenous vasoconstrictors. The isolated rat heart was perfused at constant flow rate (5-6 ml/min) with oxygenated Krebs-Ringer bicarbonate solution (37 degrees C, pH 7.4), and was rendered quiescent by a local injection of lidocaine to the atrio-ventricular node. Changes of perfusion pressure, indicating changes of CVR, were monitored and the cardiac effluent was collected for analysis of 6-keto PGF1 alpha and thromboxane B2 (stable metabolites of PGI2 and thromboxane A2, respectively) by radioimmunoassay. Hearts were infused with four different vasoconstrictors (i.e., serotonin, vasopressin, angiotensin II and the thromboxane A2/PGH2 mimetic, U46619). There was a linear relationship between the dose-dependent increase in CVR and PGI2 production in serotonin, U46619 and vasopressin-infused quiescent heart. Vasoconstriction induced by angiotensin II was not dose-dependent and was unrelated to PGI2 production. Thus, PGI2 is produced in response to coronary vessel constriction, presumably to mitigate the constriction. No detectable thromboxane B2 was released by any of these vasoconstrictors. Partial inhibition (approximately 50%) of PGI2 production by aspirin (5.6 microM) treatment resulted in a paradoxically decreased vasoconstriction except at the lowest level of serotonin and vasopressin. Aspirin (1 mM) greatly reduced PGI2 production (approximately 90%) but the fall in CVR persisted.(ABSTRACT TRUNCATED AT 250 WORDS)
原位心脏会接触到血液中携带的血管收缩剂（如血管加压素），如果不受抑制，这些物质可能会导致冠状动脉血管阻力（CVR）急剧增加。内源性血管舒张剂如前列环素（PGI2）的释放是一种可能的缓解机制。我们研究了心脏在接触外源性血管收缩剂时将CVR维持在狭窄范围内的能力。将离体大鼠心脏以恒定流速（5 - 6毫升/分钟）用含氧的 Krebs - Ringer 碳酸氢盐溶液（37℃，pH 7.4）灌注，并通过向房室结局部注射利多卡因使其静止。监测灌注压力的变化以指示CVR的变化，并收集心脏流出液，通过放射免疫测定法分析6 - 酮 - PGF1α和血栓素B2（分别为PGI2和血栓素A2的稳定代谢产物）。给心脏输注四种不同的血管收缩剂（即血清素、血管加压素、血管紧张素II以及血栓素A2/PGH2模拟物U46619）。在血清素、U46619和血管加压素灌注的静止心脏中，CVR的剂量依赖性增加与PGI2产生之间存在线性关系。血管紧张素II诱导的血管收缩不具有剂量依赖性，且与PGI2产生无关。因此，PGI2是在冠状动脉血管收缩时产生的，推测是为了减轻这种收缩。这些血管收缩剂均未释放出可检测到的血栓素B2。用阿司匹林（5.6微摩尔）处理部分抑制（约50%）PGI2产生，除了在血清素和血管加压素的最低水平外，反而导致血管收缩异常降低。阿司匹林（1毫摩尔）大大降低了PGI2产生（约90%），但CVR的下降仍然持续。（摘要截短于250字）
