Clauss François, Charloux Anne, Piquard François, Doutreleau Stéphane, Talha Samy, Zoll Joffrey, Lugnier Claire, Geny Bernard
EA3072, Translational Medicine Federation, Institute of Physiology, University of Strasbourg, 67000, Strasbourg, France.
Department of Physiology and Functional Explorations, Pôle de Pathologie thoracique, CHRU Hôpitaux Universitaires, BP 426, 67091, Strasbourg Cedex, France.
Fundam Clin Pharmacol. 2015 Aug;29(4):352-61. doi: 10.1111/fcp.12124. Epub 2015 May 25.
We investigated whether myocardial infarction (MI) enhances renal phosphodiesterases (PDE) activities, investigating particularly the relative contribution of PDE1-5 isozymes in total PDE activity involved in both cGMP and cAMP pathways, and whether angiotensin-converting enzyme inhibition (ACEi) decreases such renal PDE hyperactivities. We also investigated whether ACEi might thereby improve atrial natriuretic peptide (ANP) efficiency. We studied renal cortical PDE1-5 isozyme activities in sham (SH)-operated, MI rats and in MI rats treated with perindopril (ACEi) 1 month after coronary artery ligation. Circulating atrial natriuretic peptide (ANP), its second intracellular messenger cyclic guanosine monophosphate (cGMP) and cGMP/ANP ratio were also determined. Cortical cGMP-PDE2 (80.3 vs. 65.1 pmol/min/mg) and cGMP-PDE1 (50.7 vs. 30.1 pmol/min/mg), and cAMP-PDE2 (161 vs. 104.1 pmol/min/mg) and cAMP-PDE4 (307.5 vs. 197.2 pmol/min/mg) activities were higher in MI than in SH rats. Despite increased ANP plasma level, ANP efficiency tended to be decreased in MI compared to SH rats. Perindopril restored PDE activities and tended to improve ANP efficiency in MI rats. One month after coronary ligation, perindopril treatment of MI rats prevents the increase in renal cortical PDE activities. This may contribute to increase renal ANP efficiency in MI rats.
我们研究了心肌梗死（MI）是否会增强肾磷酸二酯酶（PDE）的活性，特别研究了PDE1 - 5同工酶在参与cGMP和cAMP途径的总PDE活性中的相对贡献，以及血管紧张素转换酶抑制（ACEi）是否会降低这种肾PDE的过度活性。我们还研究了ACEi是否可能因此提高心房利钠肽（ANP）的效率。我们研究了假手术（SH）组、MI大鼠以及冠状动脉结扎1个月后用培哚普利（ACEi）治疗的MI大鼠肾皮质PDE1 - 5同工酶的活性。还测定了循环心房利钠肽（ANP）、其细胞内第二信使环磷酸鸟苷（cGMP）以及cGMP/ANP比值。MI大鼠的皮质cGMP - PDE2（80.3对65.1 pmol/min/mg）和cGMP - PDE1（50.7对30.1 pmol/min/mg），以及cAMP - PDE2（161对104.1 pmol/min/mg）和cAMP - PDE4（307.5对197.2 pmol/min/mg）活性高于SH大鼠。尽管MI大鼠的ANP血浆水平升高，但与SH大鼠相比，MI大鼠的ANP效率仍有降低趋势。培哚普利可恢复MI大鼠的PDE活性，并倾向于提高其ANP效率。冠状动脉结扎1个月后，对MI大鼠进行培哚普利治疗可防止肾皮质PDE活性增加。这可能有助于提高MI大鼠的肾ANP效率。
