Negative metabolic effects of cGMP are enhanced in obese rat hearts.
Negative metabolic effects of cGMP are enhanced in obese rat hearts.
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cGMP 的负面代谢作用在肥胖大鼠心脏中增强。
DOI：
10.1097/01.fjc.0000159658.71051.e8
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发表时间：
2005
影响因子：
3
通讯作者：
Scholz,PeterM
中科院分区：
文献类型：
--
作者：
Weiss,HarveyR;Katz,Elizabeth;Tse,James;Scholz,PeterM
瘦素抵抗导致肥胖，并可能影响对第二信使cGMP的反应。我们验证了瘦素抵抗动物对cGMP的心肌负代谢反应会增强的假设。在麻醉的开胸Zucker肥胖大鼠（n= 16）和年龄匹配的对照大鼠（n= 13）中验证了这一假设。冠状动脉血流（微球）和o2提取（显微分光光度法）测定心肌o2消耗（VO 2）。测定cGMP蛋白激酶磷酸化和cAMP磷酸二酯酶活性。体（生理盐水）或8-Br-cGMP （10 - 3 M）局部应用于左心室表面。肥胖大鼠的体重显著增加（523±17比322±12 g）。两组间血流动力学无差异。瘦大鼠（52±13 mL o2 /min/100 g）与肥胖大鼠（54±9）的VO 2无差异。8-Br-cGMP显著降低肥胖大鼠（35±6）的VO 2，而非瘦大鼠（45±7）的VO 2。这与cGMP蛋白激酶改变的蛋白磷酸化无关。环GMP抑制瘦心脏cAMP磷酸二酯酶活性，而非肥胖心脏。由此可见，cGMP对瘦肉大鼠高心肌耗氧量的影响不显著，而对肥胖心脏的影响明显减小。这似乎与cGMP对Zucker肥胖大鼠cAMP磷酸二酯酶活性的抑制作用降低有关。
Leptin resistance leads to obesity and may affect responses to the second messenger cGMP. We tested the hypothesis that the myocardial negative metabolic response to cGMP would be enhanced in leptin-resistant animals. This hypothesis was tested in anesthetized open-chest Zucker obese (n= 16) and age-matched control rats (n= 13). Coronary blood flow (microspheres) and O 2 extraction (microspectrophotometry) measurements were used to determine myocardial O 2 consumption (VO 2). Protein phosphorylation by cGMP protein kinase and cAMP phosphodiesterase activity were also determined. Either vehicle (saline) or 8-Br-cGMP (10− 3 M) was topically applied to the left ventricular surface. Body weight was significantly greater in the obese rats (523±17 versus 322±12 g). There were no hemodynamic differences between groups. There was no difference in VO 2 between lean (52±13 mL O 2/min/100 g) and obese (54±9) vehicle-treated rats. 8-Br-cGMP significantly lowered VO 2 in obese (35±6) but not lean (45±7) rats. This was not related to altered protein phosphorylation by the cGMP protein kinase. Cyclic GMP inhibited cAMP phosphodiesterase activity in lean but not obese hearts. Thus, the high myocardial oxygen consumption of lean rats was not significantly affected by cGMP but was reduced in obese hearts. This appeared to be related to a reduced inhibition of cAMP phosphodiesterase activity by cGMP in the Zucker obese rat.