A Study on the Effect of Nitric Oxide on Myocardial Oxygen Consumption and Cardiac Contractility

一氧化氮对心肌耗氧量和心肌收缩力影响的研究

• 批准号: 10670623
• 负责人: OKUMURA Ken
• 金额: $ 1.66万
• 依托单位: HIROSAKI UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670623/
• 关键词: nitric oxide; cardiac contractility; Emax; coronary blood flow; FK409; Papaverine; cyclic GMP

We have shown that inhibition of endogenous nitric oxide (NO) augments cardiac contractility assessed by Emax, whereas others showed that spontaneous NO donors evoke a positive inotropic effect. FK409 decomposes and releases NO spontaneously when dissolved in phosphate buffer solution at 37℃. We examined the effects of FK409 and 8-bromoguanosine-cyclic-monophosphate (8-Br-cGMP) on Emax in α-chloralose-anesthetized dogs instrumented for measurements of left ventricular (LV) pressure and volume and coronary blood flow (CBF) in the left anterior descending artery (LAD). FK409, 8-Br-cGMP or papaverine was infused into the LAD, and Emax was determined by transient inferior vena cava occlusion when CBF was increased and reached its peak. Neither drug affected heart rate or LV pressure just before the measurement of Emax. FK409 increased CBF and decreased Emax in a dose-dependent manner. 8-Br-cGMP increased CBF and decreased Emax in a dose-dependent manner. Papaverine increased mean CBF but did not affect Emax. In conclusion, NO attenuates cardiac contractility in vivo, while increasing CBF. This effect seems to be mediated by cyclic-guanosine monophosphate, a second messenger of NO.

我们的研究表明，抑制内源性一氧化氮（NO）可以增强Emax评估的心脏收缩力，而其他研究则表明，自发一氧化氮供体可以激发正性肌力效应。FK409在37℃溶解于磷酸盐缓冲液中，自发分解释放NO。我们研究了FK409和8-溴鸟苷-环-单磷酸（8-Br-cGMP）对α-氯醛麻醉犬左心室（LV）压力、容积和左前降支（LAD）冠状动脉血流量（CBF） Emax的影响。在LAD内注入FK409、8-Br-cGMP或罂粟碱，在CBF升高并达到峰值时，通过短暂性下腔静脉闭塞法测定Emax。在测量Emax之前，两种药物都没有影响心率或左室压。FK409以剂量依赖性方式增加CBF并降低Emax。8-Br-cGMP以剂量依赖性方式增加CBF并降低Emax。罂粟碱增加平均脑血流，但不影响Emax。综上所述，NO在体内可减弱心脏收缩力，同时增加CBF。这种作用似乎是由一氧化氮的第二信使环鸟苷单磷酸介导的。

项目成果

Ken Okumura et al: "Study on the relationship between plasma nitric and nitrate level and salt sensitivity in human hypertension"Circulation. (in press). (2000)

Ken Okumura等人：“人类高血压中血浆硝酸盐和硝酸盐水平与盐敏感性关系的研究”循环。

Matsunaga T, Okumura K, Tsunoda R, et al.: "Role of adenosine in regulation of coronary flow in dogs with inhibited synthesis of endothelium-derived nitric oxide."Am J Physiol. 270. H427-H434 (1996)

Matsunaga T、Okumura K、Tsunoda R 等人：“腺苷在狗冠脉血流调节中的作用，可抑制内皮源性一氧化氮的合成。”Am J Physiol。

Ken Okumura.: "Influence of chronic nitric oxide inhibition of coronary blood flow regulation" Jpn Circ J. 62-5. 371-278 (1998)

Ken Okumura.：“慢性一氧化氮抑制对冠状动脉血流调节的影响”Jpn Circ J. 62-5。

Matsunaga T, Okumura K, Ishizaka H, et al.: "Effect of cumulative dose of NG-nitro-L-arginine methyl ester on coronary blood flow of anesthetized and conscious dogs."Arch Int Pharmacody. 327. 251-265 (1994)

Matsunaga T、Okumura K、Ishizaka H 等人：“NG-硝基-L-精氨酸甲酯累积剂量对麻醉和清醒狗冠状动脉血流的影响。”Arch Int Pharmacody。

Osanai T, Kamada T, Okumura K, et al.: "A novel inhibitory effect on prostacyclin synthesis of coupling factor 6 extracted from the heart of spontaneously hypertensive rats."J Biol Chem. 27. 31778-31783 (1998)

Osanai T、Kamada T、Okumura K 等人：“从自发性高血压大鼠心脏中提取的耦合因子 6 对前列环素合成具有新的抑制作用。”J Biol Chem。