No abstract

Candesartan can prevent the promotion of AF by suppressing the development of structural remodeling.

Background-The blockade of angiotensin II (Ang II) formation has protective effects on cardiovascular tissue; however, the role of Ang II in atrial electrical remodeling is unknown. The purpose of this study was to investigate the effects of candesartan and captopril on atrial electrical remodeling. Methods and Results-In 24 dogs, the atrial effective refractory period (AERP) was measured before, during, and after rapid atrial pacing. Rapid atrial pacing at 800 bpm was maintained for 180 minutes. The infusion of saline (nϭ8), candesartan (nϭ5), captopril (nϭ6), or Ang II (nϭ5) was initiated 30 minutes before rapid pacing and continued throughout the study. In the saline group, AERP was significantly shortened during rapid atrial pacing (from 149Ϯ11 to 132Ϯ16 ms, PϽ0.01). There was no significant difference in AERP shortening between the saline group and the Ang II group. However, in the candesartan and captopril groups, shortening of the AERP after rapid pacing was completely inhibited (from 142Ϯ9 to 147Ϯ12 ms with candesartan, from 153Ϯ15 to 153Ϯ14 ms with captopril, PϭNS). Although rate adaptation of the AERP was lost in the saline group, this phenomenon was preserved in the candesartan and captopril groups. Conclusions-The inhibition of endogenous Ang II prevented AERP shortening during rapid atrial pacing. These results indicate for the first time that Ang II may be involved in the mechanism of atrial electrical remodeling and that the blockade of Ang II may lead to the better therapeutic management of human atrial fibrillation. (Circulation.

Abstract-Locally formed angiotensin II (Ang II) and mast cells may participate in the development of atherosclerosis.Chymase, which originates from mast cells, is the major Ang II-forming enzyme in the human heart and aorta in vitro.The aim of the present study was to investigate aortic Ang II-forming activity (AIIFA) and the histochemical localization of each Ang II-forming enzyme in the atheromatous human aorta. Specimens of normal (nϭ9), atherosclerotic (nϭ8), and aneurysmal (nϭ6) human aortas were obtained at autopsy or cardiovascular surgery from 23 subjects (16 men, 7 women). The total, angiotensin-converting enzyme (ACE)-dependent, and chymase-dependent AIIFAs in aortic specimens were determined. The histologic and cellular localization of chymase and ACE were determined by immunocytochemistry. Total AIIFA was significantly higher in atherosclerotic and aneurysmal lesions than in normal aortas. Most of AIIFA in the human aorta in vitro was chymase-dependent in both normal (82%) and atherosclerotic aortas (90%). Immunocytochemical staining of the corresponding aortic sections with antichymase, antitryptase or anti-ACE antibodies showed that chymase-positive mast cells were located in the tunica adventitia of normal and atheromatous aortas, whereas ACE-positive cells were localized in endothelial cells of normal aorta and in macrophages of atheromatous neointima. The density of chymase-and tryptase-positive mast cells in the atherosclerotic lesions was slightly but not significantly higher than that in the normal aortas, and the number of activated mast cells in the aneurysmal lesions (18%) was significantly higher than in atherosclerotic (5%) and normal (1%) aortas. Our results suggest that local Ang II formation is increased in atherosclerotic lesions and that chymase is primarily responsible for this increase. The histologic localization and potential roles of chymase in the development of atherosclerotic lesions appear to be different from those of ACE. (Hypertension. 1999;33:1399-1405.)

These electrophysiological features, which are manifestations of the abnormal atrial electrophysiology, would favor production of atrial reentry in chronic lone AF.