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oai:docta.ucm.es:20.500.14352/986622025-03-18T15:08:15Zcom_20.500.14352_14col_20.500.14352_15

Early regression of coronary artery remodeling with esmolol and DDAH/ADMA pathway in hypertensive rats Quintana Villamandos, María Begoña Arnalich Montiel, Ana Arribas, Silvia Lüneburg, Nicole Böger, Rainer Delgado Martos, María Jesús Fernández Criado, Carmen Delgado Baeza, Emilio González, María del Carmen 615.01/.03 ADMA Coronary artery Esmolol Remodeling Spontaneously hypertensive rat Ciencias Biomédicas 32 Ciencias Médicas 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 arteryremodeling 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 thisregression. Fourteen-month-old male SHRs were treated intravenously with vehicle (SHR,n=15) or esmolol (SHR-E,n=20)(300μgkg−1min−1). Age-matched, vehicle-treated male Wistar-Kyoto rats (WKY,n=15) served as controls. SHRs were alsotreated 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, 10−9–3×10−5mol l−1) were constructed. ADMA concentrations inplasma and left ventricle and DDAH activity in tissue were analyzed. Wall thickness and cross-sectional area were significantlylower after treatment with esmolol in SHR-E than in SHR. Media thickness and smooth muscle cell count were lower in SHR-Ethan 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 contractingresponses to 5-HT. We found significantly lower ADMA levels and significantly higher DDAH activity in the ventricle in SHR-Ethan in SHR. The protective effect of esmolol on the regression of left anterior descending artery remodeling may be related tothe reduction in ADMA levels. Depto. de Farmacología y Toxicología Fac. de Medicina TRUE pub 2024-02-05T09:03:02Z 2024-02-05T09:03:02Z 2016-06-02 journal article VoR https://hdl.handle.net/20.500.14352/98662 0916-9636 10.1038/hr.2016.57 eng restricted access application/pdf Springer Nature