Relation of cyclic nucleotide ratios to ischemic and reperfusion injury in nitric oxide-donor treated rat hearts
Relation of cyclic nucleotide ratios to ischemic and reperfusion injury in nitric oxide-donor treated rat hearts
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DOI：
10.1097/00005344-200110000-00005
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发表时间：
2001-10-01
影响因子：
3
通讯作者：
Opie, LH
中科院分区：
文献类型：
--
作者：
Du Toit, EF;Meiring, J;Opie, LH
在缺血期间给予一氧化氮(NO)供体可能通过增加组织环磷酸鸟苷(CGMP)和降低胞浆Cat_1水平来保护心肌。然而，NO供体也会升高缺血的环磷酸腺苷(CAMP)水平，从而加剧缺血再灌注损伤。作者认为，抑制NO供体诱导的cAMP增加将改善这些化合物的心脏保护特性。用硝普钠(SNP，0.1 mM)或三硝酸甘油(GTN，1.0 mM)和/或腺苷环化酶(SQ，50 mU)或鸟苷酸环化酶(ODQ，30-300 mU)抑制剂，处理40分钟低流量(0.2ml/min)缺血大鼠心脏。对照再灌注率-压力乘积(RPP)恢复率为47+/-3%(n=9)，SNP治疗后RPP恢复率为59+/-1%(n=11)(p<；0.05)。缺血ODQ治疗使RPP恢复率下降至33+/-3%(n=10)(p<；0.05)。ODQ消除了SNP的心脏保护作用(RPP恢复率：40+/-5%[n=7]比59+/-1%[p<；0.05])。腺酰环化酶抑制使RPP回收率从59+/-1%(SNP)提高到72+/-4%(SNP+SQ)(n=11)(p<；0.05)。作者得出的结论是：(A)抑制NO供体诱导的缺血cGMP水平(ODQ)升高可加重再灌注RPP，(B)抑制NO供体诱导的缺血cAMP水平(SQ)进一步改善NO供体处理心脏的再灌流RPP，以及(C)NO供体处理心脏的缺血再灌注损伤程度与缺血组织cGMP水平呈负相关，而往往与缺血组织cAMP/cGMP比率直接相关。
Nitric oxide (NO) donors given during ischemia possibly protect the myocardium by increasing tissue cyclic guanosine monophosphate (cGMP) and decreasing cytosolic Cat, levels. However, NO donors also elevate ischemic cyclic adenosine monophosphate (CAMP) levels, which exacerbates ischemic-reperfusion injury. The authors propose that suppression of this NO donor-induced increase in cAMP would improve the cardioprotective properties of these compounds. Langendorff pet-fused rat hearts were treated with sodium nitroprusside (SNP, 0.1 mM) or glyceryl trinitrate (GTN, 1.0 muM and/or adenylyl cyclase (SQ, 50 muM) or guanylyl cyclase (ODQ, 30-300 muM) inhibitors during 40-min low-flow (0.2 ml/min) ischemia. Control reperfusion rate-pressure product (RPP) recoveries were 47 +/- 3% (n = 9) and improved to 59 +/- 1% (n = 11) (p < 0.05) with SNP treatment. Ischemic ODQ treatment decreased RPP recovery to 33 +/- 3% (n = 10) (p < 0.05). ODQ eliminated the cardioprotective effects of SNP (RPP recovery: 40 +/- 5% [n = 7] vs. 59 +/- 1% [p < 0.05]). Adenylyl cyclase inhibition improved RPP recovery from 59 +/- 1% (SNP) to 72 +/- 4% (SNP + SQ) (n = 11) (p < 0.05). The authors conclude that (a) suppression of the NO donor-induced elevations in ischemic cGMP levels (ODQ) worsened reperfusion RPP, (b) suppression of the NO donor-induced elevation in ischemic cAMP levels (SQ) further improved reperfusion RPP in NO donor-treated hearts, and (c) the severity of ischemic-reperfusion injury in the NO donor-treated heart was inversely related to ischemic-tissue cGMP levels and often directly related to the ischemic-tissue cAMP-to-cGMP ratio.