Cyclic GMP protein kinase mediates negative metabolic and functional effects of cyclic GMP in control and hypertrophied rabbit cardiac myocytes
Cyclic GMP protein kinase mediates negative metabolic and functional effects of cyclic GMP in control and hypertrophied rabbit cardiac myocytes
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DOI：
10.1097/00005344-199908000-00008
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发表时间：
1999-08-01
影响因子：
3
通讯作者：
Weiss, HR
中科院分区：
文献类型：
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作者：
Straznicka, M;Gong, G;Weiss, HR
我们测试了这样的假设：在分离的心肌细胞中，环磷酸鸟苷 (GMP) 的负面代谢和功能影响是由环 GMP 蛋白激酶活性介导的，并且这些影响在肾高血压张力（肾、单夹、1K1C）心脏肥大兔中发生改变。通过使用来自对照和1K1C兔子的分离心肌细胞，收集耗氧量（Mvo（2）；O-2 nl/min/10（5）细胞）、循环CMP（fmol/10（5）细胞）和细胞缩短（百分比）数据（a）在基线； tb) 与环 GMP 蛋白激酶抑制剂 KT5823 (10 (-6) M) 或 Rp-8-pCPT-cGMP (5 x 10 (-6) M) 一起使用； (c)使用环GMP磷酸二酯酶抑制剂扎普司特(10(-6)、10(-4)M)； (d) 与扎普司特 (10(-6)、10(-4) M) 和蛋白激酶抑制剂一起使用。对照组与 1K1C 肌细胞的循环 GMP 基础水平相似（62 +/- 10 与 66 +/- 17 pmol/10(5) 肌细胞）。 Zaprinast 在对照和 1K1C 肌细胞中产生剂量依赖性的环 GMP 增加。 KT5823的添加并没有显着影响环GMP水平。在对照和 1K1C 中，Zaprinast 显着且剂量依赖性地降低 Mvo(2)，而 KT5823 部分恢复它。 Zaprinast 还显着降低了缩短百分比，而 KT5823 在控制下部分恢复了缩短百分比。使用 Rp-8-pCPT-cGMP 获得了类似的结果，尽管在没有扎普司特的情况下这两种抑制剂都无效。肥大的肌细胞对所有药物表现出相当的反应。这些数据表明，环 GMP 蛋白激酶活性在基础条件下并不显着；然而，在细胞内环鸟苷酸增加的条件下，环鸟苷酸蛋白激酶在对照和1K1C肌细胞中的重要性是显着的。
We tested the hypothesis that in isolated cardiac myocytes, the negative metabolic and functional effects of cyclic guanosine monophosphate (GMP) are mediated by cyclic GMP protein kinase activity, and that these effects are altered in renal hypertensive tone-kidney, one-clip, 1K1C) cardiac hypertrophic rabbits. By using isolated cardiac myocytes from control and 1K1C rabbits, oxygen consumption (Mvo(2); O-2 nl/ min/10(5) cells), cyclic CMP (fmol/10(5) cells), and cell shortening (percentage) data were collected (a) at baseline; tb) with cyclic GMP protein kinase inhibitors KT5823 (10(-6) M) or Rp-8-pCPT-cGMP (5 x 10(-6) M); (c) with the cyclic GMP phos phodiesterase inhibitor zaprinast (10(-6), 10(-4) M); and (d) with zaprinast (10(-6), 10(-4) M) and protein kinase inhibitors. Basal levels of cyclic GMP were similar in control versus 1K1C myocytes (62 +/- 10 vs. 66 +/- 17 pmol/10(5) myocytes). Zaprinast produced a dose-dependent increase in cyclic GMP in both control and 1K1C myocytes. The addition of KT5823 did not significantly affect cyclic GMP levels. Zaprinast significantly and dose dependently decreased Mvo(2), and KT5823 partially restored it in control and 1K1C. Zaprinast also significantly decreased percentage shortening, and KT5823 partially restored it in control. Similar results were obtained with Rp-8-pCPT-cGMP, although neither inhibitor was effective without zaprinast. The hypertrophied myocytes demonstrated comparable responses to all agents. These data suggest that the cyclic GMP protein kinase activity was not significant under basal conditions; however, the importance of cyclic GMP protein kinase in control and 1K1C myocytes was significant under conditions of increased intracellular cyclic GMP.