Akatsuka Y, Egashira K, Katsuda Y, Narishige T, Ueno H, Shimokawa H, Takeshita A
Research Institute of Angiocardiology and Cardiovascular Clinic, Kyushu University School of Medicine, Fukuoka, Japan.
Cardiovasc Res. 1994 Jun;28(6):906-11. doi: 10.1093/cvr/28.6.906.
The aim was to determine a role of ATP sensitive potassium (KATP) channels in adenosine A2 receptor mediated coronary vasodilatation in anaesthetised dogs in vivo.
Coronary blood flow in the left circumflex coronary artery, aortic pressure, and left ventricular pressure were measured during intracoronary infusions of the drugs into the left circumflex artery.
A non-selective A2 receptor agonist NECA (5'-N-ethylcarboxamidoadenosine) at 10(-10)-10(-8) mol.min-1 before and after an A1 receptor antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine) increased coronary blood flow in a dose dependent manner, without affecting other haemodynamic variables. Glibenclamide at 10 micrograms.kg-1.min-1, which did not alter baseline haemodynamic variables, markedly inhibited the increases in coronary blood flow caused by NECA alone and after DPCPX (p < 0.01). A non-selective adenosine receptor antagonist 8-phenyltheophylline abolished the NECA induced increases in coronary blood flow after DPCPX. These results suggest that A2 receptor mediated coronary vasodilatation was mediated largely by opening of KATP channels. Glibenclamide did not alter the increase in coronary blood flow evoked by forskolin or acetylcholine, suggesting that KATP channels may not be involved in coronary vasodilatation induced by activation of adenylate cyclase or guanylate cyclase. Furthermore, DPCPX increased basal coronary blood flow, which was blocked by 8-phenyltheophylline and by glibenclamide, suggesting that it may have unmasked A2 receptor mediated coronary vasodilatation by inhibiting the A1 receptor mediated vasoconstricting action of endogenous adenosine.
Opening of KATP channels may be involved importantly in adenosine A2 receptor mediated coronary vasodilatation in canine hearts.
旨在确定三磷酸腺苷敏感性钾（KATP）通道在体内麻醉犬的腺苷A2受体介导的冠状动脉舒张中的作用。
在左旋冠状动脉内输注药物期间，测量左旋冠状动脉的冠状动脉血流量、主动脉压力和左心室压力。
在A1受体拮抗剂DPCPX（8-环戊基-1,3-二丙基黄嘌呤）前后，非选择性A2受体激动剂NECA（5'-N-乙基羧酰胺腺苷）以10（-10）-10（-8）mol·min-1的剂量依赖性增加冠状动脉血流量，而不影响其他血流动力学变量。10μg·kg-1·min-1的格列本脲未改变基线血流动力学变量，但显著抑制了NECA单独使用以及DPCPX使用后引起的冠状动脉血流量增加（p<0.01）。非选择性腺苷受体拮抗剂8-苯基茶碱消除了DPCPX后NECA诱导的冠状动脉血流量增加。这些结果表明，A2受体介导的冠状动脉舒张主要是通过KATP通道的开放介导的。格列本脲未改变福斯可林或乙酰胆碱引起的冠状动脉血流量增加，表明KATP通道可能不参与由腺苷酸环化酶或鸟苷酸环化酶激活诱导的冠状动脉舒张。此外，DPCPX增加了基础冠状动脉血流量，这被8-苯基茶碱和格列本脲阻断，表明它可能通过抑制内源性腺苷的A1受体介导的血管收缩作用而揭示了A2受体介导的冠状动脉舒张。
KATP通道的开放可能在犬心脏中腺苷A2受体介导的冠状动脉舒张中起重要作用。
