Ioannou P, Talesnik J
Eur J Pharmacol. 1984 Nov 27;106(3):515-29. doi: 10.1016/0014-2999(84)90055-4.
Isolated perfused hearts of rats or guinea pigs reacted to bolus doses of arachidonic acid (AA) with a coronary constriction followed by a protracted vasodilatation phase. Glyceryl trinitrate (GTN; 55-95 microM) produced coronary dilatation during which the AA-induced constriction remained unaltered, or even enhanced. After 'acute tolerance' developed by sustained GTN infusion, the constrictor phase of AA was inhibited while the vasodilatation continued unaltered or slightly enhanced. Nitroprusside (Np; 5-56 microM) determined a coronary vasodilatation that persisted throughout its administration and appeared to be associated with an inhibition of the AA-induced coronary constriction. While withdrawal of Np resulted in an immediate recovery of coronary flow levels and of the reactions to AA, the blockade of AA-coronary constriction continued after GTN withdrawal. Tranylcypromine (TRC) infusion did not alter the basal coronary flow, but it produced a specific inhibition of the AA-induced coronary vasodilatation. We postulated that the blockade of the coronary constriction exerted during GTN acute tolerance would result from an inhibition of the synthesis of a constrictor metabolite (thromboxane-like substance?) formed in the coronaries through the cyclooxygenase metabolic pathway of AA.
大鼠或豚鼠的离体灌注心脏对大剂量花生四烯酸（AA）的反应是先出现冠状动脉收缩，随后是长时间的血管舒张期。硝酸甘油（GTN；55 - 95微摩尔）可引起冠状动脉舒张，在此期间AA诱导的收缩保持不变，甚至增强。在通过持续输注GTN产生“急性耐受性”后，AA的收缩期受到抑制，而血管舒张期持续不变或略有增强。硝普钠（Np；5 - 56微摩尔）可引起冠状动脉舒张，这种舒张在给药过程中持续存在，并且似乎与抑制AA诱导的冠状动脉收缩有关。虽然停用Np会导致冠状动脉血流水平和对AA的反应立即恢复，但停用GTN后对AA冠状动脉收缩的阻断仍持续存在。反苯环丙胺（TRC）输注不会改变基础冠状动脉血流，但它会特异性抑制AA诱导的冠状动脉舒张。我们推测，GTN急性耐受性期间冠状动脉收缩的阻断是由于抑制了通过AA的环氧化酶代谢途径在冠状动脉中形成的一种收缩性代谢产物（类血栓素物质？）的合成。
