Early regression of coronary artery remodeling with esmolol and DDAH/ADMA pathway in hypertensive rats

• Published in: Hypertension research 2016-10, Vol.39 (10), p.692-700
• Main Authors: Quintana-Villamandos, Begoña, Arnalich-Montiel, Ana, Arribas, Silvia, Lüneburg, Nicole, Böger, Rainer H, Delgado-Martos, María Jesús, Fernández-Criado, Carmen, Delgado-Baeza, Emilio, González, María Carmen
• Format: Article
• Language: English
• Subjects: Adrenergic beta-1 Receptor Antagonists - pharmacokinetics; Amidohydrolases - metabolism; Animals; Arginine - analogs & derivatives; Arginine - metabolism; Blood Pressure - drug effects; Coronary Vessels - drug effects; Coronary Vessels - metabolism; Coronary Vessels - pathology; Dose-Response Relationship, Drug; Hypertension - metabolism; Hypertension - pathology; Male; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - metabolism; Nitric Oxide - metabolism; Propanolamines - pharmacology; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Serotonin - pharmacology; Vascular Remodeling - drug effects; Vascular Remodeling - physiology
• ISSN: 0916-9636; 1348-4214
• DOI: 10.1038/hr.2016.57

Our preclinical study demonstrated that esmolol produces early regression of left ventricular hypertrophy in arterial hypertension. The aim of this study was to assess the effects of short-term esmolol therapy on the regression of left anterior descending artery remodeling in spontaneously hypertensive rats (SHRs), and to determine whether the asymmetric dimethylarginine (ADMA)/dimethylarginine dimethylaminohydrolase (DDAH) pathway, a regulator of nitric oxide (NO) bioavailability, accounted for this regression. Fourteen-month-old male SHRs were treated intravenously with vehicle (SHR, n=15) or esmolol (SHR-E, n=20) (300 μg kg  min ). Age-matched, vehicle-treated male Wistar-Kyoto rats (WKY, n=15) served as controls. SHRs were also treated with nitroglycerin (SHR-N, n=5). After 48 h, the left anterior descending artery structure and morphology were assessed, and dose-response curves for 5-hydroxytryptamine (5-HT, 10 -3 × 10 mol l ) were constructed. ADMA concentrations in plasma and left ventricle and DDAH activity in tissue were analyzed. Wall thickness and cross-sectional area were significantly lower after treatment with esmolol in SHR-E than in SHR. Media thickness and smooth muscle cell count were lower in SHR-E than in SHR. Esmolol induced a significant reduction in adventitial cell count in SHR-E. The area under the concentration-response curves was significantly higher in SHR than in SHR-E, as were the esmolol normalized coronary artery contracting responses to 5-HT. We found significantly lower ADMA levels and significantly higher DDAH activity in the ventricle in SHR-E than in SHR. The protective effect of esmolol on the regression of left anterior descending artery remodeling may be related to the reduction in ADMA levels.