Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, One Shields Avenue, Davis, CA, 95616, USA.
Sci Rep. 2019 May 3;9(1):6899. doi: 10.1038/s41598-019-43318-z.
Pulmonary hypertension (PH) is a common clinical condition associated with morbidity and mortality in both humans and dogs. Sildenafil, a phosphodiesterase-5 (PDE5) inhibitor causing accumulation of cGMP, is frequently used for treatment of PH. The authors previously reported a PDE5A:E90K polymorphism in dogs that results in lower basal cyclic guanosine monophosphate (cGMP) concentrations than in wild-type dogs, which could contribute to variability in the efficacy of sildenafil. In this study, response to sildenafil therapy was evaluated in dogs with PH by comparing echocardiographic parameters, quality-of-life (QOL) score, and plasma cGMP concentrations before and after sildenafil therapy. Overall, tricuspid regurgitation estimated systolic pressure gradient (PG) and QOL score were significantly improved after sildenafil therapy, and the plasma cGMP concentration was significantly decreased. Dogs that had a heterozygous PDE5A status had a significantly worse QOL score when compared to the wildtype group after sildenafil treatment. The simple and multiple regression analyses revealed a significant but weak prediction for the percent reduction in QOL score with sildenafil treatment by plasma cGMP level and by the PDE5A:E90K polymorphic status. This study showed that sildenafil treatment improved PH in dogs, and the PDE5A:E90K polymorphism blunted the efficacy of sildenafil in terms of QOL improvement.
肺动脉高压（PH）是一种常见的临床病症，与人类和犬类的发病率和死亡率都有关。西地那非是一种磷酸二酯酶-5（PDE5）抑制剂，可导致 cGMP 的积累，常用于治疗 PH。作者之前曾报道过犬的 PDE5A：E90K 多态性，与野生型犬相比，其基础环磷酸鸟苷（cGMP）浓度更低，这可能导致西地那非疗效的差异。在这项研究中，通过比较接受西地那非治疗前后的超声心动图参数、生活质量（QOL）评分和血浆 cGMP 浓度，评估了 PH 犬对西地那非治疗的反应。总体而言，在接受西地那非治疗后，三尖瓣反流估测收缩期压力梯度（PG）和 QOL 评分显著改善，血浆 cGMP 浓度显著降低。与野生型组相比，杂合子 PDE5A 状态的犬在接受西地那非治疗后 QOL 评分明显更差。简单和多元回归分析显示，血浆 cGMP 水平和 PDE5A：E90K 多态性状态对 QOL 评分的西地那非治疗百分比降低有显著但较弱的预测作用。本研究表明，西地那非治疗可改善犬的 PH，而 PDE5A：E90K 多态性则降低了西地那非在改善 QOL 方面的疗效。
