Gul Rukhsana, Bazighifan Arwa, Nawaz Shahid, Alfadda Assim A
Obesity Research Center, College of Medicine, King Saud University, P.O. Box 2925, Riyadh, 11461, Saudi Arabia.
Department of Medicine, College of Medicine, King Saud University, P.O. Box 2925, Riyadh, 11461, Saudi Arabia.
BMC Pharmacol Toxicol. 2025 Aug 4;26(1):142. doi: 10.1186/s40360-025-00970-8.
Mitochondrial dysfunction and oxidative stress induced by overactivation of angiotensin II (Ang II) are major contributors to the progression of cardiovascular diseases (CVD). This study investigates the comparative effects of nebivolol, a third-generation β1-adrenergic blocker, and metoprolol, a second-generation β1-adrenergic blocker, on Ang II-induced mitochondrial impairment in H9c2 cardiomyoblasts.
Nebivolol and metoprolol mediated protective effects were demonstrated against Ang II-induced mitochondrial dysfunction in H9c2 cells. Intracellular reactive oxygen species (ROS) production was assessed by detecting 2',7'-dichlorofluorescein (DCF) fluorescence. Western blotting and Real-time PCR were used to quantify protein and mRNA levels, respectively.
Our results showed that both nebivolol and metoprolol significantly attenuated Ang II-induced ROS generation and the expression of apoptotic and proinflammatory genes. However, nebivolol demonstrated higher efficacy than metoprolol in suppressing the expression of the proapoptotic marker BNIP3, while upregulating the antioxidant defense system and anti-apoptotic BCL2 expression. Additionally, nebivolol enhanced the mitochondrial biogenesis and fusion related gene expression.
In conclusion, both nebivolol and metoprolol effectively reduce oxidative stress and expression of proinflammatory genes in response to Ang II. However, nebivolol provides increased protection by restoring the antioxidant defense system and mitochondrial functions, highlighting its potential therapeutic advantage in Ang II-induced cardiac pathology.
血管紧张素 II（Ang II）过度激活所诱导的线粒体功能障碍和氧化应激是心血管疾病（CVD）进展的主要促成因素。本研究调查了第三代β1肾上腺素能阻滞剂奈必洛尔和第二代β1肾上腺素能阻滞剂美托洛尔对Ang II诱导的H9c2心肌母细胞线粒体损伤的比较作用。
证实了奈必洛尔和美托洛尔对Ang II诱导的H9c2细胞线粒体功能障碍具有介导的保护作用。通过检测2',7'-二氯荧光素（DCF）荧光来评估细胞内活性氧（ROS）的产生。分别使用蛋白质印迹法和实时定量聚合酶链反应来定量蛋白质和mRNA水平。
我们的结果表明，奈必洛尔和美托洛尔均显著减弱了Ang II诱导的ROS生成以及凋亡和促炎基因的表达。然而，在抑制促凋亡标志物BNIP3的表达方面，奈必洛尔显示出比美托洛尔更高的效力，同时上调抗氧化防御系统和抗凋亡BCL2的表达。此外，奈必洛尔增强了线粒体生物合成和融合相关基因的表达。
总之，奈必洛尔和美托洛尔均能有效减轻Ang II诱导的氧化应激和促炎基因的表达。然而，奈必洛尔通过恢复抗氧化防御系统和线粒体功能提供了更强的保护，突出了其在Ang II诱导的心脏病理中的潜在治疗优势。
