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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Positive inotropy due to lowering cyclic GMP is also mediated by increases in cyclic AMP in control and hypertrophic hearts.
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Positive inotropy due to lowering cyclic GMP is also mediated by increases in cyclic AMP in control and hypertrophic hearts.

机译：在控制性和肥厚性心脏中，由于环状AMP降低而导致的正性肌力也被介导。

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摘要

The aim of the current study was to determine if lowering myocardial cyclic GMP by guanylate cyclase inhibition would add independently to the positive inotropic effects caused by raising cyclic AMP and if these effects are modified in left ventricular hypertrophy (LVH) produced by aortic valve plication. Isoproterenol (ISO) (0.1 mg x kg(-1) x min(-1)) was infused into a branch of the left anterior descending coronary artery of seven control and eight hypertrophy open-chest anesthetized dogs. After 10 min, simultaneous infusion of methylene blue (MB) (2 mg x kg(-1) x min(-1)) was initiated at the same site. Hypertrophy increased heart weight and heart weight/body weight ratio. While both drugs increased left ventricular dP/dt(max), no additional global effects were observed in either group. Changes in regional variables followed the same pattern in both groups, i.e., ISO produced an increase that was enhanced by the addition of MB. ISO increased segment shortening, with a significant change in the control group. ISO increased regional force in both groups. The addition of MB increased force above ISO levels, with a significant change in the LVH group. ISO increased regional minute work (g x mm x min(-1)) (control, 1779 +/- 428 to 2541 +/- 500; LVH, 1157 +/- 253 to 1839 +/- 404) and O2 consumption. MB further increased regional work (control, 2993 +/- 952; LVH, 2416 +/- 853) and O2 consumption. ISO raised cyclic AMP (pmoles x g(-1)) (control, 468 +/- 41 to 580 +/- 84; LVH, 445 +/- 43 to 562 +/- 71) and had no effect on cyclic GMP (pmoles x g(-1)) (control, baseline 3.27 +/- 0.22, ISO 2.87 +/- 0.23; LVH, baseline 6.84 +/- 1.12, ISO 5.66 +/- 0.54). The addition of MB lowered cyclic GMP (control, 2.41 +/- 0.26; LVH, 3.68 +/- 0.35), but also increased cyclic AMP (control, 1021 +/- 121; LVH, 1107 +/- 134). Similar results were observed in control hearts using a specific soluble guanylate cyclase inhibitor (ODQ) in terms of changes in local work, O2 consumption, and cyclic nucleotides. Thus, at least part of the positive inotropic response to lowering cyclic GMP was mediated by changes in cyclic AMP in the current model. This was true in both control and LVH animals, although baseline cyclic GMP levels were higher, and a larger reduction in cyclic GMP was observed with MB in the LVH group.
机译：当前研究的目的是确定通过鸟苷酸环化酶抑制降低心肌循环GMP是否会独立增加由循环AMP升高引起的正性肌力作用，以及这些作用是否在由主动脉瓣折叠所产生的左心室肥大（LVH）中得到改变。将异丙肾上腺素（ISO）（0.1 mg x kg（-1）x min（-1））注入7只对照和8只肥大的开胸麻醉狗的左前降支的分支中。 10分钟后，在同一位置开始同时输注亚甲蓝（MB）（2 mg x kg（-1）x min（-1））。肥大会增加心脏重量和心脏重量/体重比。虽然两种药物均增加左心室dP / dt（max），但两组均未观察到其他总体作用。两组中区域变量的变化遵循相同的模式，即ISO产生的增加通过添加MB得以增强。 ISO增加了节段的缩短，对照组发生了重大变化。 ISO在两组中都增加了地区力量。 MB的增加使力量超过了ISO水平，LVH组发生了显着变化。 ISO增加了区域分钟工作量（g x mm x min（-1））（对照，1779 +/- 428至2541 +/- 500; LVH，1157 +/- 253至1839 +/- 404）和O2消耗量。 MB进一步增加了区域工作（控制2993 +/- 952; LVH，2416 +/- 853）和氧气消耗。 ISO提高的循环AMP（pmoles xg（-1））（对照，468 +/- 41至580 +/- 84; LVH，445 +/- 43至562 +/- 71），对循环GMP（pmoles）无影响xg（-1））（对照，基线3.27 +/- 0.22，ISO 2.87 +/- 0.23; LVH，基线6.84 +/- 1.12，ISO 5.66 +/- 0.54）。 MB的添加降低了循环GMP（对照，2.41 +/- 0.26; LVH，3.68 +/- 0.35），但也增加了循环AMP（对照，1021 +/- 121; LVH，1107 +/- 134）。就局部功，O2消耗和环状核苷酸的变化而言，使用特异性可溶性鸟苷酸环化酶抑制剂（ODQ）在对照心脏中观察到相似的结果。因此，在当前模型中，对降低循环GMP的正性肌力反应至少有一部分是由循环AMP的变化介导的。尽管基线循环GMP水平较高，并且在LVH组中MB观察到循环GMP降低较大，但在对照组和LVH动物中均是如此。

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