Department of Physiology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand.
Department of Physiology, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
Life Sci. 2023 Sep 1;328:121929. doi: 10.1016/j.lfs.2023.121929. Epub 2023 Jul 10.
New drugs for heart failure (HF) that target restoring the impaired NO-sGC-cGMP pathway are being developed. We aimed to investigate the effects of vericiguat, an sGC stimulator, on cardiac function, blood pressure (BP), cardiac mitochondrial quality, and cardiac fibrosis in rat models of chronic mitral regurgitation (MR).
We surgically induced MR in 20 Sprague-Dawley rats and performed sham procedures on 10 rats (negative control). Four weeks post-surgery, we randomly divided the MR rats into two groups: MR group and MR + vericiguat group. Vericiguat (0.5 mg/kg, PO) was administered once a day via oral gavage for 8 weeks, while the sham and MR groups received equivalent volumes of drinking water instead. We took echocardiography and BP measurements at baseline (4 weeks post-surgery) and at the end of study (8 weeks after treatment). At the study end, all rats were euthanized and their hearts were immediately collected, weighed, and used for histopathology and mitochondrial quality assessments.
Vericiguat preserved cardiac functions and structural remodeling in the MR rats, with significantly lower systolic BPs than baseline values (P < 0.05). Additionally, vericiguat significantly improved the mitochondrial quality by attenuating ROS production, depolarization and swelling when comparing the values in both groups (P < 0.05). The fibrosis area also significantly decreased in the MR + vericiguat group (P < 0.05).
Vericiguat demonstrated cardioprotective effects on cardiac function, BP, and fibrosis by preserving mitochondrial quality in rats with HF due to MR.
目前正在开发针对恢复受损的 NO-sGC-cGMP 途径的心力衰竭（HF）新药。我们旨在研究可溶性鸟苷酸环化酶（sGC）刺激剂维立西呱对慢性二尖瓣反流（MR）大鼠模型中心脏功能、血压（BP）、心脏线粒体质量和心脏纤维化的影响。
我们通过手术在 20 只 Sprague-Dawley 大鼠中诱导 MR，并在 10 只大鼠（阴性对照）中进行假手术。手术后 4 周，我们将 MR 大鼠随机分为两组：MR 组和 MR+维立西呱组。维立西呱（0.5mg/kg，PO）每天通过口服灌胃给药 1 次，持续 8 周，而假手术和 MR 组则给予等量的饮用水。我们在基线（手术后 4 周）和研究结束时（治疗 8 周后）进行超声心动图和 BP 测量。在研究结束时，所有大鼠被安乐死，立即采集心脏，称重，并用于组织病理学和线粒体质量评估。
维立西呱可维持 MR 大鼠的心脏功能和结构重塑，与基线值相比，收缩压明显降低（P<0.05）。此外，与对照组相比，维立西呱通过减少 ROS 产生、线粒体去极化和肿胀来显著改善线粒体质量（P<0.05）。MR+维立西呱组的纤维化面积也显著减少（P<0.05）。
维立西呱通过在 MR 导致 HF 的大鼠中维持线粒体质量，显示出对心脏功能、BP 和纤维化的心脏保护作用。
