A study of mechanism in atrial fibrillation

为探讨环核苷酸在心房颤动（AF）发生和/或持续中的作用，测定了电诱发AF犬血浆环磷酸鸟苷（c-GMP）和环磷酸腺苷（c-AMP）水平，并测定了静脉注射二丁酰环磷酸鸟苷衍生物（Dbc-GMP）对心房颤动阈值（AFT）的影响。同时测定了阵发性房颤和窦性心律患者血浆c-GMP、c-AMP和心钠素（ANP）水平。c-GMP水平在房颤发作后15 min即显著升高，并在实验过程中逐渐升高。Dbc-GMP诱导AFT呈剂量依赖性降低。临床评估显示，房颤患者的c-GMP和ANP水平几乎是窦性心律患者的4倍。结果提示，c-GMP的升高在AF的维持和/或发生中起重要作用。 ...更多信息 89例心脏病患者的平均肺动脉压和右心房直径相关。结果提示，心房压力升高和心房扩张均能引起血浆ANP浓度升高，hANP舒张犬冠状动脉，并呈剂量依赖性地增加组织c-GMP水平。结果表明，hNAP通过直接激活冠状动脉平滑肌鸟苷酸环化酶而舒张冠状动脉。双丁酰环磷酸腺苷和双丁酰环磷酸鸟苷对心钠素释放无影响。精氨酸加压素和苯肾上腺素刺激ANP释放呈剂量依赖性。钙调素拮抗剂W-7和蛋白激酶C抑制剂H-7可抑制苯肾上腺素刺激的ANP释放。心房牵张刺激心钠素释放，但释放不被W-7或H-7抑制。这些结果表明，负责拉伸诱导的心钠素释放的机制不同于苯肾上腺素诱导的心钠素释放。少

To investigate the role of cyclic nucleotides in the genesis and/or the persistence of atrial fibrillation (AF), plasma levels of cyclic GMP (c-GMP) and cyclic AMP (c-AMP) were measured in dogs with electrically induced AF. The atrial fibrillation threshold (AFT) after intravenous administration of a dibutyryl derivative of c-GMP (Dbc-GMP) on AFT were determined. Plasma levels of c-GMP, c-AMP and atrial natriuretic peptide (ANP) were also measured in patients during paroxysmal AF and sinus rhythm. The c-GMP level increased significantly 15 min after the onset of artificial AF, and gradually increased during the course of the experiment. Dbc-GMP induced a dose- dependent decrease in AFT. Clinical assessment revealed that patients had almost four times higher c-GMP and ANP levels during AF than during sinus rhythm. These results suggest that the increase in c-GMP plays an important role in the maintenance and/or the genesis of AF.Plasma concentrations of ANP and c-GMP were significantly … More correlated with mean pulmonary arterial pressure and right atrial diameter in 89 patients with heart disease. It is suggested that increased plasma concentrations of ANP were induced by increased atrial pressure as well as atrial distention in human.hANP relaxed canine coronary artery, and that increased tissue c-GMP levels in a dose-dependent fashion. The results suggest that hNAP relaxes the coronary artery by directly activating the guanylate cyclase in coronary smooth muscle.The role of intracellular signals in the regulation of ANP release was investigated using isolated rat left atria. Dibutyryl cyclic AMP and dibutyryl cyclic GMP had no effect on ANP release. Arginine vasopressin and phenylephrine stimulated ANP release dose-dependently. The ANP release stimulated by phenylephrine was inhibited by W-7, a calmodulin antagonist, and H-7, a protein kinase C inhibitor. Atrial stretch stimulated ANP release, but the release was not inhibited by W-7 or H-7. These results suggest that the mechanism responsible for stretch-induced ANP release differs from that for phenylephrine-induced ANP release. Less