García-Villalón Angel Luis, Amezquita Yesika María, Monge Luis, Fernández Nuria, Climent Belén, Sánchez Ana, Diéguez Godofredo
Departamento de Fisiología, Facultad de Medicina, Universidad Autonoma, Arzobispo Morcillo 2, Madrid 28029, Spain.
Eur J Pharmacol. 2005 Feb 21;509(2-3):165-70. doi: 10.1016/j.ejphar.2004.11.065.
The effects of the duration of ischemia on coronary vasoconstriction after ischemia-reperfusion were analysed in rat hearts. After 15, 30 or 45 min of global zero-flow ischemia and 15 min reperfusion, the coronary response to endothelin-1 (10(-10)-10(-7) M) and the thromboxane A2 analogue 9,11-dideoxy-1a,9a-epoxymethanoprostaglandin F2alpha (U46691, 10(-8)-10(-6) M) was recorded. Vasoconstriction induced by endothelin-1 only increased after short 15 min periods of ischemia. In contrast, the vasoconstriction induced by U46619 remained unmodified by short ischemias but was reduced after longer periods of ischemia (30 and 45 min). Inhibition of nitric oxide synthesis with the Nw-nitro-L-arginine methyl ester (L-NAME, 10(-4) M) augmented the vasoconstriction induced by endothelin-1 in non-ischemic hearts, but not following ischemia. Similarly, L-NAME increased the vasoconstriction induced by U46619 to a greater extent in non-ischemic hearts than following ischemia. These results suggest that ischemia-reperfusion inhibits nitric oxide production, causing an increased coronary response to endothelin-1 after brief ischemias. Longer ischemias may non-specifically inhibit coronary vasoconstriction and reduce nitric oxide production.
在大鼠心脏中分析了缺血持续时间对缺血再灌注后冠状动脉血管收缩的影响。在进行15、30或45分钟的全心零流量缺血及15分钟再灌注后，记录冠状动脉对内皮素-1（10⁻¹⁰ - 10⁻⁷M）和血栓素A2类似物9,11-二脱氧-1α,9α-环氧甲撑前列腺素F2α（U46691，10⁻⁸ - 10⁻⁶M）的反应。仅在短暂的15分钟缺血后，内皮素-1诱导的血管收缩增加。相比之下，U46619诱导的血管收缩在短暂缺血后未改变，但在较长时间缺血（30和45分钟）后降低。用Nω-硝基-L-精氨酸甲酯（L-NAME，10⁻⁴M）抑制一氧化氮合成可增强非缺血心脏中内皮素-1诱导的血管收缩，但缺血后则不然。同样，L-NAME在非缺血心脏中比缺血后更大程度地增加U46619诱导的血管收缩。这些结果表明，缺血再灌注抑制一氧化氮生成，导致短暂缺血后冠状动脉对内皮素-1的反应增强。较长时间的缺血可能非特异性地抑制冠状动脉血管收缩并减少一氧化氮生成。
