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 ± 33 versus AUCSHR = 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 (10−6 to 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.

Short-Term Treatment with Esmolol Reverses Left Ventricular Hypertrophy in Adult Spontaneously Hypertensive Rats via Inhibition of Akt/NF-κB and NFATc4

“…In a previous study, our group has demonstrated that, compared with SHR, plasma superoxide anion scavenging activity (including superoxide dismutase) was more pronounced in SHR-E and this was associated with an improvement in nitric oxide availability measured as nitrites/nitrates [ 37 ]. In the present study, short-term administration of esmolol restored catalase activity to the level detected in WKY controls.…”

Coronary microvascular disease as an early culprit in the pathophysiology of diabetes and metabolic syndrome

“…septal coronary artery) or different methods of assessing vascular structure- histology (50, 51) vs . pressure myograph (52, 53). Thus, for future studies, it is imperative to differentiate and understand the differences between the coronary macrovascular (e.g.…”

“…Additionally, asymmetric dimethylarginine (ADMA) – an endogenous inhibitor of NO- was increased in hypertensive animals and associated with aortic and coronary microvascular remodeling (53, 61). The decrease in ADMA was associated with attenuation of vascular remodeling of aorta and coronary artery, through an increase in NO bioavailability and superoxide dismutase (SOD) activity (52, 53, 61). …”

The comparative effects of esmolol and amiodarone on isolated coronary artery bypass grafts

“…This effect is particularly obvious in arterial grafts and is of interest for RA grafts, since this conduit is notorious for its susceptibility to vasospasms. The possible mechanism of this acute vasodilatory effect is nitric oxide (NO)-dependent vasodilatation as explained by Arnalich-Montiel et al, who demonstrated that esmolol induces acetylcholine-mediated NO-dependent vasodilatation in the coronaries of hypertensive rats (15). Similarly, in an in vivo human study of coronary arteries, esmolol infusion was shown to increase the minimal luminal diameter and decrease the endothelial shear stress in patients with moderate coronary stenosis (16).…”