Zofenopril exerts a cardiovascular protective effect on rats infused with angiotensin II beyond angiotensin-converting enzyme inhibition

OBJECTIVES: 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. METHODS: 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. KEY FINDINGS: 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. CONCLUSION: Zofenopril could exert additional beneficial effects beyond ACE inhibition that would justify the improvement of pathophysiological processes triggered by angiotensin II.