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Cardiovascular changes in spontaneously hypertensive rats are improved by chronic treatment with zofenopril
Author(s) -
GómezRoso M,
Montero MJ,
Carrón R,
Sevilla MA
Publication year - 2009
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2009.00491.x
Subject(s) - medicine , blood pressure , sodium nitroprusside , spontaneously hypertensive rat , endocrinology , vascular smooth muscle , left ventricular hypertrophy , muscle hypertrophy , aorta , chemistry , nitric oxide , smooth muscle
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 (Z 0.5 and Z 10 ) 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.