Department of Anesthesiology, Reanimation and Intensive Care, Hospital General Universitario Gregorio Marañón, 28007 Madrid, Spain.
Department of Pharmacology and Toxicology, Universidad Complutense de Madrid, 28040 Madrid, Spain.
Biomed Res Int. 2019 Jul 2;2019:6374582. doi: 10.1155/2019/6374582. eCollection 2019.
Dronedarone is recommended for the treatment of atrial fibrillation. However, we do not know its effect on vascular remodeling. This study was designed to assess whether dronedarone has the potential to improve the intramyocardial artery remodeling induced by chronic hypertension. Ten-month-old male spontaneously hypertensive rats (SHR) were randomly assigned to receive dronedarone (100 mg/kg) or vehicle. Age-matched male Wistar-Kyoto rats served as controls. After 14 days of treatment, we studied the structure (geometry and fibrosis) of the intramyocardial artery using histological analysis. Nitric oxide (NO) in plasma was analyzed. In the untreated SHR, we observed a significant increase in external diameter, lumen diameter, wall width, cross-sectional area, and collagen volume density, as was expected in the experimental model. Dronedarone induced a significant decrease in wall width, cross-sectional area, and collagen volume density in SHR-D in comparison with untreated SHR. The values obtained in SHR-D were similar in the WKY control group. We found significantly higher NO levels in plasma in SHR-D than in untreated SHR. Dronedarone improves the intramyocardial artery remodeling induced by chronic hypertension in SHR through increased nitric oxide bioavailability.
多非利特被推荐用于治疗心房颤动。然而，我们不知道它对血管重塑的影响。本研究旨在评估多非利特是否有潜力改善慢性高血压引起的心肌内动脉重塑。10 月龄雄性自发性高血压大鼠（SHR）被随机分为多非利特（100mg/kg）组或对照组。年龄匹配的雄性 Wistar-Kyoto 大鼠作为对照组。治疗 14 天后，我们使用组织学分析研究了心肌内动脉的结构（几何形状和纤维化）。分析了血浆中的一氧化氮（NO）。在未治疗的 SHR 中，正如实验模型所预期的那样，我们观察到外径、管腔直径、壁宽、截面积和胶原体积密度显著增加。与未治疗的 SHR 相比，多非利特使 SHR-D 的壁宽、截面积和胶原体积密度显著降低。SHR-D 的这些值与 WKY 对照组相似。我们发现 SHR-D 中的血浆 NO 水平明显高于未治疗的 SHR。多非利特通过增加一氧化氮的生物利用度改善了 SHR 慢性高血压引起的心肌内动脉重塑。
