Cardiology Section, VA Salt Lake City Health Care System, and Departments of Internal Medicine (Cardiology) and Pharmacology & Toxicology, University of Utah, Salt Lake City, UT, USA.
Curr Opin Pharmacol. 2011 Dec;11(6):707-13. doi: 10.1016/j.coph.2011.09.001. Epub 2011 Sep 28.
In dilated cardiomyopathy, a condition characterized by chamber enlargement and reduced myocardial contractility, decreases in β-adrenergic receptor density and increases in Gαi and β-adrenergic receptor kinase activities attenuate the stimulation of adenylyl cyclase in response to catecholamines. PDE3 inhibitors have been used to 'overcome' the reduction in cAMP generation by blocking cAMP hydrolysis. These drugs increase contractility in the short-term, but long-term administration leads to an increase in mortality that correlates with an increase in sudden cardiac death. Whether separate mechanisms account for these beneficial and harmful effects, and, if so, whether PDE3 can be targeted so as to increase contractility without increasing mortality are questions that remain unanswered.
在扩张型心肌病中，一种以心室扩大和心肌收缩力降低为特征的疾病，β-肾上腺素能受体密度降低和 Gαi 和β-肾上腺素能受体激酶活性增加，减弱了儿茶酚胺对腺苷酸环化酶的刺激。 PDE3 抑制剂已被用于通过阻断 cAMP 水解来“克服” cAMP 生成的减少。这些药物在短期内增加收缩力，但长期给药会导致死亡率增加，与心脏性猝死增加相关。是否有不同的机制解释这些有益和有害的影响，如果是，是否可以针对 PDE3 增加收缩力而不增加死亡率，这些问题仍未得到解答。
