Gómez-Roso Miriam, Montero María J, Carrón Rosalía, Sevilla María A
Department of Physiology and Pharmacology, Faculty of Pharmacy, University of Salamanca, Salamanca, Spain.
J Pharm Pharmacol. 2016 Nov;68(11):1422-1429. doi: 10.1111/jphp.12641. Epub 2016 Sep 27.
Elevated levels of angiotensin II are implicated in the hypertensive pathophysiological process. Zofenopril has a sulphydryl group which gives it antioxidant properties. The aim of this study was to investigate its beneficial effects beyond angiotensin-converting enzyme (ACE) inhibition using angiotensin II-infused rats as hypertension model.
Zofenopril was added in drinking water. Systolic blood pressure was assessed by the tail-cuff method. Left ventricular weight/body weight ratio was calculated as cardiac hypertrophy index. An estimate of the cardiac collagen was performed by measuring the content of hydroxyproline. Vascular reactivity was evaluated on aortic rings and isolated perfused kidney, and vascular structure in thoracic aorta was studied. Superoxide anion generation was quantified in aorta by lucigenin-enhanced chemiluminescence.
Zofenopril partially prevented the increase in systolic blood pressure and cardiac hypertrophy induced by angiotensin II and avoided the increase in collagen deposition. The treatment improved vasorelaxing responses, reversed the vascular remodelling and abolished the effects of angiotensin II on the production of ·O2-. It is worth to mention that all these results are observed even with high levels of plasma angiotensin.
Zofenopril could exert additional beneficial effects beyond ACE inhibition that would justify the improvement of pathophysiological processes triggered by angiotensin II.
血管紧张素II水平升高与高血压病理生理过程有关。佐芬普利含有巯基，具有抗氧化特性。本研究的目的是使用输注血管紧张素II的大鼠作为高血压模型，研究其在抑制血管紧张素转换酶（ACE）之外的有益作用。
将佐芬普利添加到饮用水中。采用尾套法评估收缩压。计算左心室重量/体重比作为心脏肥大指数。通过测量羟脯氨酸含量来估计心脏胶原蛋白。在主动脉环和离体灌注肾脏上评估血管反应性，并研究胸主动脉的血管结构。通过光泽精增强化学发光法对主动脉中的超氧阴离子生成进行定量。
佐芬普利部分预防了血管紧张素II诱导的收缩压升高和心脏肥大，并避免了胶原蛋白沉积增加。该治疗改善了血管舒张反应，逆转了血管重塑，并消除了血管紧张素II对·O2-产生的影响。值得一提的是，即使在血浆血管紧张素水平较高的情况下也观察到了所有这些结果。
佐芬普利除了抑制ACE之外，还可能发挥额外的有益作用，这可以解释其对血管紧张素II引发的病理生理过程的改善作用。
