Neely C F, Haile D M, Cahill B E, Kadowitz P J
Department of Anesthesia, University of Pennsylvania School of Medicine, Philadelphia.
J Pharmacol Exp Ther. 1991 Sep;258(3):753-61.
It has been reported recently that adenosine and ATP produce dose- and tone-dependent responses in the feline pulmonary vascular (PV) bed. The present study was undertaken to investigate the mechanisms mediating vasoconstrictor (VC) responses to adenosine and ATP in the intact-chest, spontaneously breathing cat under conditions of controlled blood flow and constant left atrial pressure. The order of potency of adenosine receptor agonists to produce VC in the PV bed was the selective adenosine A1 receptor agonist R-phenylisopropyladenosine greater than the mixed A1, A2 receptor agonist, adenosine greater than the selective adenosine A2 receptor agonist, 2-phenylaminoadenosine. The dose-related increase in lobar arterial pressure in response to adenosine was blocked by an adenosine (P1) receptor antagonist, BWA1433U, the cyclooxygenase inhibitor, meclofenamate, and the thromboxane A2 receptor antagonist, SQ29548. The order of potency of ATP analogs to produce VC in the PV bed was alpha,beta-methylene ATP (alpha,beta-meATP) much greater than beta,tau-methylene ATP greater than ATP. BWA1433U inhibited VC responses to ATP without affecting responses to its degradation-resistant analogs beta,tau-methylene ATP and alpha,beta-meATP. In the presence of BWA1433U and a continuous intralobar infusion of the selective 5'-nucleotidase inhibitor, alpha,beta-methyleneadenosine-5'-diphosphate, ATP VC responses are significantly enhanced compared to those after BWA1433U. alpha,beta-Methyleneadenosine-5'-diphosphate had no effect on the VC response to U44069 after BWA1433U. Meclofenamate significantly inhibited the vasoconstrictor responses to ATP but not to alpha,beta-meATP.(ABSTRACT TRUNCATED AT 250 WORDS)
最近有报道称，腺苷和三磷酸腺苷（ATP）在猫肺血管（PV）床中产生剂量和张力依赖性反应。本研究旨在探讨在控制血流和恒定左心房压力的条件下，完整胸腔、自主呼吸的猫中，介导对腺苷和ATP血管收缩（VC）反应的机制。腺苷受体激动剂在PV床中产生VC的效力顺序为：选择性腺苷A1受体激动剂R-苯异丙基腺苷大于混合A1、A2受体激动剂腺苷大于选择性腺苷A2受体激动剂2-苯氨基腺苷。腺苷（P1）受体拮抗剂BWA1433U、环氧化酶抑制剂甲氯芬那酸和血栓素A2受体拮抗剂SQ29548可阻断腺苷引起的叶动脉压力剂量相关增加。ATP类似物在PV床中产生VC的效力顺序为：α,β-亚甲基ATP（α,β-meATP）远大于β,τ-亚甲基ATP大于ATP。BWA1433U抑制对ATP的VC反应，而不影响对其抗降解类似物β,τ-亚甲基ATP和α,β-meATP的反应。在BWA1433U存在且叶内持续输注选择性5'-核苷酸酶抑制剂α,β-亚甲基腺苷-5'-二磷酸的情况下，与BWA1433U处理后相比，ATP的VC反应显著增强。α,β-亚甲基腺苷-5'-二磷酸对BWA1433U处理后对U44069的VC反应无影响。甲氯芬那酸显著抑制对ATP的血管收缩反应，但对α,β-meATP无影响。（摘要截断于250字）
