Short-Term Esmolol Improves Coronary Artery Remodeling in Spontaneously Hypertensive Rats through Increased Nitric Oxide Bioavailability and Superoxide Dismutase Activity

Abstract

The aim of this study was to assess the effects of short-term esmolol therapy on coronary artery structure and function and plasma oxidative stress in spontaneously hypertensive rats (SHR). For this purpose, 14-month-old male SHR were treated for 48 hours with esmolol (SHR-E, 300 μg/kg/min). Age-matched untreated male SHR and Wistar Kyoto rats (WKY) were used as hypertensive and normotensive controls, respectively. At the end of intervention we performed a histological study to analyze coronary artery wall width (WW), wall-to-lumen ratio (W/L), and media cross-sectional area (MCSA). Dose-response curves for acetylcholine (ACh) and sodium nitroprusside were constructed. We also assessed several plasma oxidative stress biomarkers, namely, superoxide scavenging activity (SOSA), nitrites, and total antioxidant capacity (TAC). We observed a significant reduction in WW (P<0.001), W/L (P<0.05), and MCSA (P<0.01) and improved endothelium-dependent relaxation (AUCSHR-E=201.2±33versusAUCSHR=97.5±21,P<0.05) in SHR-E compared with untreated SHR; no differences were observed for WW, MCSA, and endothelium-dependent relaxation by ACh at higher concentrations (10−6to 10−4 mol/l) for SHR-E with respect to WKY. SOSA (P<0.001) and nitrite (P<0.01) values were significantly higher in SHR-E than in untreated SHR; however, TAC did not increase after treatment with esmolol. Esmolol improves early coronary artery remodeling in SHR.