A study of mechanism in atrial fibrillation

为了研究环核苷酸在房颤（AF）发生和/或持续中的作用，我们测量了电致AF狗的血浆中环GMP （c-GMP）和环AMP （c-AMP）的水平，并测定了在AF上静脉注射c-GMP二丁基衍生物（Dbc-GMP）后心房颤动阈值（AFT）。同时测定阵发性房颤和窦性心律患者的血浆c-GMP、c-AMP和心房钠素（ANP）水平。人工房颤发作后15 min， c-GMP水平显著升高，并在实验过程中逐渐升高。Dbc-GMP诱导了AFT的剂量依赖性下降。临床评估显示，患者在AF期间的c-GMP和ANP水平几乎是窦性心律期间的四倍。89例心脏病患者血浆ANP和c-GMP浓度与平均肺动脉压和右房内径有显著相关性，表明c-GMP的升高在af的维持和/或发生中起重要作用。提示ANP的血药浓度升高是由心房压力升高和心房扩张引起的。hANP使犬冠状动脉松弛，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中的鸟苷酸环化酶使冠状动脉松弛。利用离体大鼠左心房研究细胞内信号在ANP释放调控中的作用。二丁基环AMP和二丁基环GMP对ANP的释放无影响。精氨酸加压素和苯肾上腺素刺激ANP释放呈剂量依赖性。苯肾上腺素刺激的ANP释放被钙调素拮抗剂W-7和蛋白激酶C抑制剂H-7所抑制。心房拉伸刺激ANP释放，但W-7和H-7不抑制ANP释放。这些结果表明，拉伸诱导的ANP释放机制与苯肾上腺素诱导的ANP释放机制不同。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