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Abstract：
The important regulator of cardiac function, cAMP, is hydrolyzed by different cyclic nucleotide phosphodiesterases (PDEs), whose expression and activity are not uniform throughout the heart. Of these enzymes, PDE2 shapes β1 adrenoceptor-dependent cardiac cAMP signaling, both in the right and left ventricular myocardium, but its role in regulating β2 adrenoceptor-mediated responses is less well known. Our aim was to investigate possible differences in PDE2 transcription and activity between right (RV) and left (LV) rat ventricular myocardium, as well as its role in regulating β2 adrenoceptor effects. The free walls of the RV and the LV were obtained from Sprague-Dawley rat hearts. Relative mRNA for PDE2 (quantified by qPCR) and PDE2 activity (evaluated by a colorimetric procedure and using the PDE2 inhibitor EHNA) were determined in RV and LV. Also, β2 adrenoceptor-mediated effects (β2-adrenoceptor agonist salbutamol + β1 adrenoceptor antagonist CGP-20712A) on contractility and cAMP concentrations, in the absence or presence of EHNA, were studied in the RV and LV. PDE2 transcript levels were less abundant in RV than in LV and the contribution of PDE2 to the total PDE activity was around 25% lower in the microsomal fraction of the RV compared with the LV. β2 adrenoceptor activation increased inotropy and cAMP levels in the LV when measured in the presence of EHNA, but no such effects were observed in the RV, either in the presence or absence of EHNA. These results indicate interventricular differences in PDE2 transcript and activity levels, which may distinctly regulate β2 adrenoceptor-mediated contractility and cAMP concentrations in the RV and in the LV of the rat heart.
摘要：
心脏功能的重要调节因子,cAMP,由不同的环核苷酸磷酸二酯酶（PDEs）水解，他们的表达和活动在整个心脏中是不一致的。在这些酶中，PDE2形成β1肾上腺素受体依赖性心脏cAMP信号，右心室和左心室心肌，但其在调节β2肾上腺素受体介导的反应中的作用尚不为人所知。我们的目的是研究右（RV）和左（LV）大鼠心室心肌之间PDE2转录和活性的可能差异，以及它在调节β2肾上腺素受体作用中的作用。RV和LV的自由壁是从Sprague-Dawley大鼠心脏获得的。在RV和LV中测定PDE2的相对mRNA(通过qPCR定量)和PDE2活性(通过比色方法并使用PDE2抑制剂EHNA评估)。此外，β2肾上腺素受体介导的作用（β2-肾上腺素受体激动剂沙丁胺醇β1肾上腺素受体拮抗剂CGP-20712A）对收缩性和cAMP浓度，在EHNA不存在的情况下，在RV和LV中进行了研究。PDE2转录物水平在RV中比在LV中少,并且与LV相比,在RV的微粒体部分中PDE2对总PDE活性的贡献低约25%。当在存在EHNA的情况下测量时，β2肾上腺素受体激活会增加LV中的肌力和cAMP水平，但是在RV中没有观察到这样的影响，无论是否存在EHNA。这些结果表明PDE2转录物和活性水平的室间差异，可以明显调节大鼠心脏RV和LV中β2肾上腺素受体介导的收缩性和cAMP浓度。
