Cardiovascular changes in spontaneously hypertensive rats are improved by chronic treatment with zofenopril

Abstract

Background and purpose:The aim of this study was to investigate the effect of chronic treatment with antihypertensive and non-antihypertensive doses of zofenopril on cardiovascular changes in spontaneously hypertensive rats (SHR). Experimental approach: Male SHR were treated with 0.5 or 10 mg·kg -1 per day of zofenopril (Z0.5 and Z10) for 3 months. SHR and Wistar-Kyoto rats (WKY) receiving vehicle were used as controls. Systolic blood pressure was measured using the tail cuff method. Left ventricular weight/body weight ratio was calculated as cardiac hypertrophy index. Angiotensin converting enzyme (ACE) activity was determined in plasma and tissues by a fluorimetric method. Vascular reactivity was evaluated on aortic rings by acetylcholine and sodium nitroprusside relaxations. Effects on vascular structure were assessed by lumen diameter, wall thickness and medial cross-sectional area determination. Superoxide anion generation was quantified using lucigenin-amplified chemiluminescence in aorta. Results: Long-term daily administration of zofenopril (10 mg·kg -1 ) to SHR reduced blood pressure to WKY values, decreased cardiac hypertrophy, improved the acetylcholine-induced relaxant response and reversed the vascular remodelling. ACE inhibition and antioxidant activity were involved in these effects. 0.5 mg·kg -1 per day of zofenopril slightly modified blood pressure and the other effects were weaker. Conclusions and implications: Antihypertensive effects of chronic treatment with zofenopril were accompanied by recovery of endothelial function and improvement of cardiovascular structure. Low-dose zofenopril had little effect on blood pressure, with some benefits on cardiovascular structure and function. Inhibition of ACE and antioxidant activity were involved in these effects.

Angiotensin-converting enzyme inhibitor limits pulse-wave velocity and aortic calcification in a rat model of cystic renal disease

“…The influence of perindopril on vascular remodeling may be blood pressure dependent, or it may mediated by non-ANG II mechanisms, as ACE is responsible for both production of ANG II and degradation of the vasoactive bradykinin (10). ACE inhibitors are effective, however, in controlling vascular remodeling, independent of blood pressure, and aortic stiffening as a result of fibrosis can be reversed by ACE inhibition independent of bradykinin preservation (8,17).…”

Liver growth factor treatment restores cell-extracellular matrix balance in resistance arteries and improves left ventricular hypertrophy in SHR

“…A second limitation of this study is if a higher dose or time of treatment with LGF could have reversed to a higher extent the cardiovascular alterations in SHR. For example, it has been reported that high doses of zofenopril achieved a maximal effect after 4 wk of zofenopril treatment and were maintained over the following 4 wk, an effect that was not observed in the low-dose treatment (32). We are at initial stages of study of the cardiovascular actions of LGF, and these aspects, which have been largely analyzed in classical antihypertensive treatments, deserve further attention.…”

“…, was able to markedly improve blood pressure, LVH, vascular remodeling, and endothelial dysfunction in SHR, but a lower dose (0.5 mg·kg Ϫ1 ·day Ϫ1 ) had a weaker effect (32). Furthermore, recently discovered actions of LGF treatment on arteries from apolipoprotein E knockout mice, involving a 25% reduction of atherosclerotic lesions (65), suggest that LGF has wider cardiovascular regenerative effects.…”

Passiflora quadrangularis L. PREVENTS EXPERIMENTAL HYPERTENSION AND VASCULAR REMODELLING IN RATS EXPOSED TO NITRIC OXIDE DEFICIT

“…40 minutes). Afterwards, ACh or SNP (from 10 -10 to 10 -4 M) was added cumulatively every 30 s in aliquots of 0.5 log units of concentration (34).…”