Grover G J, Baird A J, Sleph P G
Department of Pharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000, USA.
Cardiovasc Res. 1996 Apr;31(4):511-7.
An interaction between adenosine A1 receptors and ATP-sensitive potassium channels (KATP) has been hypothesized to mediate preconditioning in several species. Unlike other species tested, KATP blockers and A1 antagonists do not abolish preconditioning in rat hearts. The purpose of this study was to determine if KATP and A1 receptors are pharmacologically linked in rat hearts as they are in other species.
Isolated rat hearts were given 0.03-1.00 microM R-PIA (adenosine A1 receptor agonist) with or without concomitant 0.3 microM glyburide starting 10 min pre-ischemia. After 25 min global ischemia, the hearts were reperfused for 30 min. Rat hearts were also treated with 1-30 microM cromakalim in the presence of 10 microM DPCPX (adenosine A1 antagonist).
R-PIA produced a concentration-dependent bradycardia before ischemia which was blocked by DPCPX. R-PIA increased the time to onset of contracture in a concentration-dependent manner (EC25 = 0.13 microM) and this was unaffected by 0.3 microM glyburide (EC25 = 0.20 microM). This concentration of glyburide completely abolished the protective effects of 10 microM cromakalim. R-PIA also significantly enhanced post-ischemic recovery of function and reduced LDH release, and glyburide did not alter these responses. Cromakalim significantly increased the time to onset of contracture (EC25 = 4.5 microM) and 10 microM DPCPX had no effect on this (EC25 = 5.6 microM). Cromakalim also significantly enhanced post-ischemic recovery of function and reduced LDH release. DPCPX did not alter these cardioprotective effects while glyburide completely abolished the cardioprotective effects of cromakalim.
While both cromakalim and R-PIA are cardioprotective in isolated rat hearts, they are not pharmacologically linked, possibly explaining why preconditioning may be different in this species.
腺苷A1受体与ATP敏感性钾通道（KATP）之间的相互作用被认为介导了几种动物的预处理效应。与其他受试动物不同，KATP阻滞剂和A1拮抗剂并不能消除大鼠心脏的预处理效应。本研究的目的是确定在大鼠心脏中，KATP和A1受体是否像在其他动物中一样存在药理学联系。
在缺血前10分钟开始，给离体大鼠心脏给予0.03 - 1.00微摩尔/升的R - PIA（腺苷A1受体激动剂），同时或不同时给予0.3微摩尔/升的格列本脲。在25分钟全心缺血后，心脏再灌注30分钟。大鼠心脏也在10微摩尔/升DPCPX（腺苷A1拮抗剂）存在的情况下用1 - 30微摩尔/升的克罗卡林处理。
R - PIA在缺血前产生浓度依赖性心动过缓，可被DPCPX阻断。R - PIA以浓度依赖性方式增加挛缩发作时间（EC25 = 0.13微摩尔/升），且不受0.3微摩尔/升格列本脲影响（EC25 = 0.20微摩尔/升）。该浓度的格列本脲完全消除了10微摩尔/升克罗卡林的保护作用。R - PIA还显著增强了缺血后功能恢复并减少了乳酸脱氢酶释放，而格列本脲并未改变这些反应。克罗卡林显著增加挛缩发作时间（EC25 = 4.5微摩尔/升），10微摩尔/升DPCPX对此无影响（EC25 = 5.6微摩尔/升）。克罗卡林也显著增强了缺血后功能恢复并减少了乳酸脱氢酶释放。DPCPX未改变这些心脏保护作用，而格列本脲完全消除了克罗卡林的心脏保护作用。
虽然克罗卡林和R - PIA在离体大鼠心脏中均具有心脏保护作用，但它们不存在药理学联系，这可能解释了该物种预处理效应为何不同。
