Sodium nitroprusside protects adult rat cardiac myocytes from cellular injury induced by simulated ischemia - Role for a non-cGMP- dependent mechanism of nitric oxide protection
Sodium nitroprusside protects adult rat cardiac myocytes from cellular injury induced by simulated ischemia - Role for a non-cGMP- dependent mechanism of nitric oxide protection
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DOI：
10.1097/01.fjc.0000189601.12276.8b
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发表时间：
2006-01-01
影响因子：
3
通讯作者：
Ritchie, RH
中科院分区：
文献类型：
--
作者：
Garreffa, AM;Woodman, OL;Ritchie, RH
一氧化氮（NO）的心脏保护作用主要归因于cGMP。然而，NO可能引起一些独立于cGMP的生物学作用。我们测试的假设，NO供体硝普钠特异性地保护分离的心肌细胞免受损伤，至少部分独立于它的能力，通过使用代谢抑制来模拟缺血，以提高cGMP。代谢抑制诱导的成年大鼠心肌细胞损伤（乳酸脱氢酶和肌酸激酶活性增加）显着降低硝普钠至少30%，在所有研究浓度（0.3-100 μ M）。硝普钠（1 μ M）增加心肌细胞cGMP含量，但既不是一个稳定的类似物cGMP（8-溴-cGMP），也不是一个强大的cGMP刺激（心房利钠肽）模仿硝普钠的保护作用。此外，可溶性鸟苷酸环化酶的抑制未能抑制硝普钠心肌细胞保护。相反，格列本脲（10 μ M）抑制ATP敏感性钾（K-ATP）通道或四乙基溴化铵（1 mM）或伊比利亚毒素（20 nM）抑制钙敏感性钾（K-Ca）通道可显著减弱硝普钠的心脏保护作用。总之，硝普钠保护分离的心肌细胞不受cGMP的代谢抑制;相反，K-Ca和K-ATP通道的抑制逆转了硝普钠的作用，从而揭示了心肌细胞中NO介导的保护的另一种机制。
The cardioprotective actions of nitric oxide (NO) have largely been attributed to cGMP. NO may, however, elicit some biological actions independently of cGMP. We tested the hypothesis that the NO donor sodium nitroprusside specifically protects isolated cardiomyocytes from injury at least in part independently of its ability to elevate cGMP by using metabolic inhibition to simulate ischemia. Metabolic inhibition-induced injury of adult rat cardiomyocytes (increased activity of lactate dehydrogenase and creatine kinase) was significantly reduced by sodium nitroprusside by at least 30% at all concentrations studied (0.3-100 mu M). Sodium nitroprusside (1 mu M) increased cardiomyocyte cGMP content, but neither a stable analogue of cGMP (8-bromo-cGMP) nor a potent cGMP stimulus (atrial natriuretic peptide) mimicked the protective effects of sodium nitroprusside. Moreover, inhibition of soluble guanylyl cyclase failed to inhibit sodium nitroprusside cardiomyocyte protection. Conversely, inhibition of either ATP-sensitive potassium (K-ATP) channels with glibenclamide (10 mu M) or calcium-sensitive potassium (K-Ca) channels with tetraethylantmonium bromide (1 mM) or iberiotoxin (20 nM) markedly attenuated the cardioprotective actions of sodium nitroprusside. In conclusion, sodium nitroprusside protects isolated cardiomyocytes from metabolic inhibition independently of cGMP; rather, inhibition of K-Ca and K-ATP channels reverses the sodium nitroprusside actions, thus unmasking another mechanism for NO-mediated protection in cardiomyocytes.