title: Early regression of coronary artery remodeling with esmolol and DDAH/ADMA pathway in hypertensive rats.
abstract: 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-1min-1). 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, 10-9-3 × 10-5mol l-1) 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.
authors.affiliation: Department of Anesthesiology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.|Department of Pharmacology, Faculty of Medicine, Universidad Complutense, Madrid, Spain.
authors.forename: Begoña
authors.initials: B
authors.lastname: Quintana-Villamandos
authors.affiliation: Department of Anesthesiology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Arnalich-Montiel
authors.affiliation: Department of Physiology, Faculty of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Arribas
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Lüneburg
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Böger
authors.affiliation: Molecular Biology Laboratory, Department of Experimental Medicine and Surgery, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Delgado-Martos
authors.affiliation: Faculty of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Fernández-Criado
authors.affiliation: Molecular Biology Laboratory, Department of Experimental Medicine and Surgery, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Delgado-Baeza
authors.affiliation: Department of Physiology, Faculty of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: María Carmen
authors.initials: MC
authors.lastname: González
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000493:pharmacokinetics*; D000581:Amidohydrolases / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012701:Serotonin / Q000494:pharmacology; D066253:Vascular Remodeling / Q000187:drug effects* / Q000502:physiology
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D011412:Propanolamines; D009569:Nitric Oxide; D012701:Serotonin; C018524:N,N-dimethylarginine; D001120:Arginine; D000581:Amidohydrolases; C059999:dimethylargininase; C036604:esmolol