Sabouni M H, Brown G L, Kotake A N, Douglas F L, Mustafa S J
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858-4354.
Eur J Pharmacol. 1990 Oct 23;187(3):525-30. doi: 10.1016/0014-2999(90)90381-f.
The antagonistic effects of CGS-15943A on the relaxations produced by adenosine and its analogs in human blood vessels were investigated in vitro. Donor hearts were the source of coronary arteries, whereas the internal mammary arteries and saphenous veins were obtained from patients undergoing coronary bypass surgery. Adenosine and its analogs, 5'-N-ethylcarboxamidoadenosine (NECA) and 2-chloroadenosine (CAD), produced concentration-dependent relaxations in KCl-contracted coronary rings. CGS-15943A antagonized, significantly, the relaxations produced by adenosine, NECA and CAD in coronary arteries. Similarly, the adenosine receptor antagonist, 8-phenyltheophylline (8PT, 10-mumol/l), caused a significant attenuation of the relaxing responses to adenosine, NECA and CAD in coronary arteries. In rings obtained from internal mammary arteries and saphenous veins, adenosine, NECA and CAD all produced concentration-dependent relaxations. These relaxations were smaller in magnitude than those obtained in coronary arteries, and were slightly greater in rings contracted with 10 mumol/l prostaglandin F2 alpha (PGF2 alpha) as compared to 35 mmol/l KCl. However, the mammary arteries and saphenous veins relaxed completely in response to 100 mumol/l papaverine. CGS-15943A (10 mumol/l) did not antagonize the relaxing effects of adenosine and its analogs in these vessels. The results show that coronary arteries are more responsive than mammary arteries or saphenous veins to the relaxing effects of adenosine analogs and that these relaxing responses are dependent on the contracting agent. Furthermore, CGS-15943A demonstrated antagonism of the adenosine response in coronary arteries.
在体外研究了CGS-15943A对腺苷及其类似物在人体血管中所产生舒张作用的拮抗效应。供体心脏是冠状动脉的来源，而乳内动脉和大隐静脉则取自接受冠状动脉搭桥手术的患者。腺苷及其类似物5'-N-乙基甲酰胺腺苷（NECA）和2-氯腺苷（CAD）在氯化钾预收缩的冠状动脉环中产生浓度依赖性舒张作用。CGS-15943A能显著拮抗腺苷、NECA和CAD在冠状动脉中所产生的舒张作用。同样，腺苷受体拮抗剂8-苯基茶碱（8PT，10 μmol/L）能显著减弱冠状动脉对腺苷、NECA和CAD的舒张反应。在取自乳内动脉和大隐静脉的血管环中，腺苷、NECA和CAD均产生浓度依赖性舒张作用。这些舒张作用的幅度小于在冠状动脉中所观察到的，并且与用35 mmol/L氯化钾预收缩相比，在用10 μmol/L前列腺素F2α（PGF2α）预收缩的血管环中稍大。然而，乳内动脉和大隐静脉对100 μmol/L罂粟碱完全舒张。CGS-15943A（10 μmol/L）并不拮抗腺苷及其类似物在这些血管中的舒张作用。结果表明，冠状动脉对腺苷类似物舒张作用的反应性比乳内动脉或大隐静脉更高，并且这些舒张反应取决于收缩剂。此外，CGS-15943A在冠状动脉中表现出对腺苷反应的拮抗作用。
