Maintenance over Time of the Effect Produced by Esmolol on the Structure and Function of Coronary Arteries in Hypertensive Heart Diseases

Abstract

We previously observed that esmolol treatment for 48 h reduced vascular lesions in spontaneously hypertensive rats (SHRs). Therefore, we investigated whether this beneficial effect is persistent after withdrawal. Fourteen-month-old SHRs (SHR-Es) were treated with esmolol (300 μg/kg/min) or a vehicle for 48 h. Two separate groups were also given identical treatment, but they were then monitored for a further 1 week and 1 month after drug withdrawal. We analyzed the geometry and composition of the coronary artery, vascular reactivity and plasma redox status. Esmolol significantly decreased wall thickness (medial layer thickness and cell count), external diameter and cross-sectional area of the artery, and this effect persisted 1 month after drug withdrawal. Esmolol significantly improved endothelium-dependent relaxation by ACh (10−9–10−4 mol/L); this effect persisted 1 week (10−9–10−4 mol/L) and 1 month (10−6–10−4 mol/L) after withdrawal. Esmolol reduced the contraction induced by 5-HT (3 × 10−8–3 × 10−5 mol/L), and this effect persisted 1 week after withdrawal (10−6–3 × 10−5 mol/L). Esmolol increased nitrates and reduced glutathione, and it decreased malondialdehyde and carbonyls; this enhancement was maintained 1 month after withdrawal. This study shows that the effect of esmolol on coronary remodeling is persistent after treatment withdrawal in SHRs, and the improvement in plasma oxidative status can be implicated in this effect.

Keywords

• esmolol
• vascular remodeling
• spontaneously hypertensive rat
• treatment withdrawal