[en] The current study was carried out to explore the effects of chronic treatment with zofenopril on the cardiovascular alterations observed during hypertension. Spontaneously hypertensive rats (SHR) were treated with 0,5 and 10 mg/kg/day of zofenopril for 2 and 3 months. The effects after two months of treatment and one month withdrawal were also studied. Untreated SHR and Wistar Kyoto were used as control.Treatment with zofenopril at 10 mg/kg/day reduced systolic blood pressure with respect to the untreated SHR group. Blood pressure was maintained without increase during the treatment period with 0.5 mg/kg/day. The antihypertensive effect was observed after drug withdrawal. This effect was accompanied by an improvement on vascular reactivity as in conductance as in resistance arteries. Cyclooxygenase-derived contracting factors and superoxide anion have a crucial role in endothelial dysfunction of SHR and zofenopril treatment was effective to neutralize the effects of both factors. Zofenopril decreased superoxide anion production in in vivo and in vitro suggesting that might prevent oxidative stress in hypertension.Zofenopril reduced heart collagen content, cardiac and renal hypertrophy and vascular remodeling that hypertension induces on conductance and resistance arteries. The high lipophilicity of zofenopril allows a higher ACE inhibition in tissues than in plasma even with low dose.Beneficial effects on endothelial dysfunction and cardiac and vascular hypertrophy observed with antihypertensive dose of zofenopril were maintained after withdrawal.In the hypertension induced by chronic infusion of angiotensin II, zofenopril partially avoided the increase in blood pressure and cardiac hypertrophy and prevented loss of vascular relaxation of ACh and the increase on heart collagen content, showing that these effects would not be totally dependent of ACE inhibition.

[es] En este trabajo se estudi? el efecto del tratamiento cr?nico con zofenopril sobre las alteraciones cardiovasculares que se presentan en la hipertensi?n arterial.Zofenopril se administr? a ratas espont?neamente hipertensas durante 2 o 3 meses a las dosis de 0,5 y 10 mg/kg/d?a y se estudi?, adem?s, si los efectos se manten?an un mes despu?s de retirar el tratamiento.A lo largo del estudio se produjo un incremento progresivo de la presi?n en los animales control que no se observ? en el grupo tratado con 0,5 mg/kg/d?a. El tratamiento con 10 mg/kg/d?a redujo la presi?n arterial sist?lica de manera significativa, efecto que se mantiene parcialmente tras la retirada del f?rmaco.El tratamiento mejor? la funcionalidad vascular, tanto en arterias de resistencia como de conductancia. Los experimentos realizados en arteria aorta indican que este efecto se debe, por una parte, a una menor contribuci?n de prostanoides contracturantes y por otra a la menor producci?n de radicales super?xido, que hemos observado tanto in vivo como in vitro .Zofenopril reduce la hipertrofia renal, la fibrosis e hipertrofia cardiaca y revierte las alteraciones de vasos de conductancia y de resistencia producidas por la hipertensi?n. Estos efectos se favorecen por la elevada lipofilia del f?rmaco que da lugar a la inhibici?n de la ECA tisular, incluso con la dosis m?s baja.La reducci?n de la hipertrofia cardiaca y vascular, as? como la mejor?a en la funci?n endotelial se mantienen tras la retirada del tratamiento con 10 mg/kg/d?a.Algunos efectos de zofenopril son independientes de su capacidad para inhibir la formaci?n de angiotensina II ya que, previene la p?rdida de relajaci?n a nivel vascular y el incremento en la deposici?n de col?geno a nivel cardiaco y evita parcialmente el incremento en la presi?n arterial sist?lica y en el ?ndice de hipertrofia cardiaca en el modelo de hipertensi?n inducida por angiotensina.