Impact of a Multichannel Blocker in Attenuating Intramyocardial Artery Remodeling in Hypertensive Rats through Increased Nitric Oxide Bioavailability.

Begoña Quintana-Villamandos,María Jesús Delgado-Martos,Emilio Delgado-Baeza

doi:10.1155/2019/6374582

Abstract

Dronedarone is recommended for the treatment of atrial fibrillation. However, we do not know its effect on vascular remodeling. This study was designed to assess whether dronedarone has the potential to improve the intramyocardial artery remodeling induced by chronic hypertension. Ten-month-old male spontaneously hypertensive rats (SHR) were randomly assigned to receive dronedarone (100 mg/kg) or vehicle. Age-matched male Wistar-Kyoto rats served as controls. After 14 days of treatment, we studied the structure (geometry and fibrosis) of the intramyocardial artery using histological analysis. Nitric oxide (NO) in plasma was analyzed. In the untreated SHR, we observed a significant increase in external diameter, lumen diameter, wall width, cross-sectional area, and collagen volume density, as was expected in the experimental model. Dronedarone induced a significant decrease in wall width, cross-sectional area, and collagen volume density in SHR-D in comparison with untreated SHR. The values obtained in SHR-D were similar in the WKY control group. We found significantly higher NO levels in plasma in SHR-D than in untreated SHR. Dronedarone improves the intramyocardial artery remodeling induced by chronic hypertension in SHR through increased nitric oxide bioavailability.

Highlights

Hypertension leads to adverse remodeling in the coronary artery wall and increases the incidence of cardiovascular events [1, 2]
Our results show that two weeks of treatment with dronedarone improves the intramyocardial artery remodeling in adult spontaneously hypertensive rats (SHR) through increased nitric oxide bioavailability
We find that antihypertensive and antiarrhythmic drugs produce regression coronary artery remodeling after chronic treatment in SHR: administration of losartan for 5 weeks reduced wall thickness and cross-sectional area (CSA), amlodipine and enalapril led to a reduction in media thickness and CSA after 12 weeks, perindopril and indapamide led to a reduction in CSA and vessel diameter after 8 weeks, and lisinopril reduced the thickness of the coronary artery media after 12 weeks [18,19,20,21]

Summary

Introduction

Hypertension leads to adverse remodeling (structural alterations) in the coronary artery wall and increases the incidence of cardiovascular events [1, 2]. Antihypertensive therapy reverses vascular structural alterations and reduces cardiovascular morbidity [3, 4]. The benefits by improving structural alterations in the coronary artery in patients with hypertension are an important factor in the selection of antihypertensive therapy [5]. Dronedarone is a novel antiarrhythmic drug for atrial fibrillation, acting as a multichannel blocker [6]. Dronedarone reduced the incidence of hospitalization due to cardiovascular events or death in patients with atrial fibrillation [7, 8]; it is avoided in patients with unstable chronic heart failure [9]. Left ventricular hypertrophy, which is the usual complication of hypertension, is associated with structural changes, namely, coronary remodeling [11]; we BioMed Research International

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