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


RESULTS
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.


CONCLUSIONS
Zofenopril could exert additional beneficial effects beyond ACE inhibition that would justify the improvement of pathophysiological processes triggered by angiotensin II.
Department of Physiology and Pharmacology, Faculty of Pharmacy, University of Salamanca, Salamanca, Spain.
Miriam
M
Gómez-Roso
Department of Physiology and Pharmacology, Faculty of Pharmacy, University of Salamanca, Salamanca, Spain.
María J
MJ
Montero
Department of Physiology and Pharmacology, Faculty of Pharmacy, University of Salamanca, Salamanca, Spain.
Rosalía
R
Carrón
Department of Physiology and Pharmacology, Faculty of Pharmacy, University of Salamanca, Salamanca, Spain. masevilla@usal.es.
María A
MA
Sevilla
D000804:Angiotensin II; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000031:analogs & derivatives* / Q000494:pharmacology; D006332:Cardiomegaly / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control*; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005355:Fibrosis; D006909:Hydroxyproline / Q000378:metabolism; D006973:Hypertension / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D014665:Vasodilator Agents; D013481:Superoxides; D000804:Angiotensin II; C044958:zofenopril; D003094:Collagen; D002216:Captopril; D006909:Hydroxyproline
angiotensin II; hypertension; remodelling; superoxide anion; vascular reactivity; zofenopril