Interaction between the opposing functional effects of cyclic AMP and cyclic GMP in hypertrophic cardiac myocytes.
Interaction between the opposing functional effects of cyclic AMP and cyclic GMP in hypertrophic cardiac myocytes.
复制标题
肥大心肌细胞中环 AMP 和环 GMP 的相反功能作用之间的相互作用。
DOI：
10.1007/s003950170075
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发表时间：
2001
影响因子：
9.5
通讯作者：
Weiss,HR
中科院分区：
文献类型：
--
作者：
Patel,KN;Yan,L;Gandhi,A;Scholz,PM;Weiss,HR
我们测试的假设，在离体心肌细胞，环磷酸鸟苷的负功能的影响将被钝化时，环磷酸腺苷的水平增加，这种相互作用将改变肾性高血压（一肾一夹，1 K1 C）心肌肥厚兔。使用分离的对照和1 K1 C心室肌细胞，收集环AMP和细胞缩短（%）数据：1）基线时，2）添加8-Br-cGMP 10−7，−6，− 5 M后，3）毛喉素（10− 6 M）和腺苷酸环化酶激活剂后，随后添加8-Br-cGMP 10−7，−6，− 5 M。对照组与1 K1 C组的基础cAMP水平相似（10.2 ± 1.6 pmol/105心肌细胞与11.3 ± 2.6 pmol/105心肌细胞）。我们发现8-Br-cGMP以剂量相关的方式降低对照心肌细胞（5.1 ± 0.6至3.2 ± 0.4%）和肥大心肌细胞（5.2 ± 0.4至3.6 ± 0.5%）的缩短百分比。8-Br-cGMP可使对照组心肌细胞cAMP含量显著增加（14.1 ± 2.1），而1 K1 C心肌细胞cAMP含量无明显变化。Forskolin使对照组心肌细胞缩短百分率增加（3.8 ± 0.1 ~ 4.8 ± 0.4），而肥大组无明显增加（3.6 ± 0.3 ~ 3.7 ± 0.3）。在对照组（13.9 ± 2.0）和1 K1 C细胞（14.6 ± 3.8）中加入forskolin后，cAMP水平均显著升高。Forskolin可减弱8-Br-cGMP对正常对照组（4.8 ± 0.4）和1 K1 C心肌细胞（3.7 ± 0.3）的负性功能效应（3.2 ± 0.1）。8-Br-cGMP对对照组（13.9 ± 2.0 ~ 14.8 ± 2.5）和1 K1 C组（14.6 ± 3.8 ~ 13.8 ± 1.9）的cAMP水平无影响。结果表明，8-Br-cGMP对肥大心肌细胞的负性功能作用与对照组相似，而cAMP的正性功能作用减弱。在对照细胞中加入8-Br-cGMP后，cAMP水平增加，但1 K1 C细胞中没有。我们的结论是，在控制和肥大的心肌细胞，环GMP的影响后，毛喉素钝化，但这似乎并不涉及环AMP磷酸二酯酶活性。
We tested the hypothesis that in isolated cardiac myocytes, the negative functional effects of cyclic GMP would be blunted when the level of cyclic AMP was increased and that this interaction would be altered in renal hypertensive (One-Kidney-One-Clip, 1K1C) cardiac hypertrophic rabbits. Using isolated control and 1K1C ventricular myocytes, cyclic AMP and cell shortening (%) data were collected: 1) at baseline, 2) after the addition of 8-Br-cGMP 10−7, −6, −5M, and 3) after forskolin (10−6M), and adenylate cyclase activator, followed by 8-Br-cGMP 10−7, −6,−5M. Basal levels of cyclic AMP were similar in control vs. 1K1C myocytes (10.2 ± 1.6 vs. 11.3 ± 2.6 pmol/105myocytes). We found that 8-Br-cGMP decreased the percent shortening in a dose related manner in both control myocytes (5.1 ± 0.6 to 3.2 ± 0.4%) and hypertrophic myocytes (5.2 ± 0.4 to 3.6 ± 0.5). The level of cyclic AMP significantly increased after the addition of 8-Br-cGMP in control myocytes (14.1 ± 2.1), but not in 1K1C myocytes. Forskolin increased the percent shortening in the control myocytes (3.8 ± 0.1 to 4.8 ± 0.4), but no significant increase was noted in the hypertrophic myocytes (3.6 ± 0.3 to 3.7 ± 0.3). The level of cyclic AMP significantly increased after the addition of forskolin in both control (13.9 ± 2.0), and 1K1C cells (14.6 ± 3.8). Forskolin attenuated the negative functional effects of 8-Br-cGMP in the control (4.8 ± 0.4 to 3.2 ± 0.1) and 1K1C myocytes (3.7 ± 0.3 to 2.7 ± 0.3). The adition of 8-Br-cGMP did not affect the level of cyclic AMP after forskolin in either control (13.9 ± 2.0 to 14.8 ± 2.5) or 1K1C myocytes (14.6 ± 3.8 to 13.8 ± 1.9). These data indicated that in hypertrophic cardiac myocytes the negative functional effects of 8-Br-cGMP were similar to control, but the positive functional effects of cyclic AMP were blunted. There was an increase in cyclic AMP levels after addition of 8-Br-cGMP in control but not 1K1C cells. We conclude that in control and hypertrophic myocytes, the effects of cyclic GMP were blunted after forskolin, but this did not seem to be related to cyclic AMP phosphodiesterase activity.