Early regression of coronary artery remodeling with esmolol and DDAH/ADMA pathway in hypertensive rats
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Early regression of coronary artery remodeling with esmolol and DDAH/ADMA pathway in hypertensive rats. / 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.
In: HYPERTENS RES, Vol. 39, No. 10, 10.2016, p. 692-700.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Early regression of coronary artery remodeling with esmolol and DDAH/ADMA pathway in hypertensive rats
AU - Quintana-Villamandos, Begoña
AU - Arnalich-Montiel, Ana
AU - Arribas, Silvia
AU - Lüneburg, Nicole
AU - Böger, Rainer H
AU - Delgado-Martos, María Jesús
AU - Fernández-Criado, Carmen
AU - Delgado-Baeza, Emilio
AU - González, María Carmen
PY - 2016/10
Y1 - 2016/10
N2 - 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-1 min-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 × 10-5 mol 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.
AB - 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-1 min-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 × 10-5 mol 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.
KW - Adrenergic beta-1 Receptor Antagonists/pharmacokinetics
KW - Amidohydrolases/metabolism
KW - Animals
KW - Arginine/analogs & derivatives
KW - Blood Pressure/drug effects
KW - Coronary Vessels/drug effects
KW - Dose-Response Relationship, Drug
KW - Hypertension/metabolism
KW - Male
KW - Myocytes, Smooth Muscle/drug effects
KW - Nitric Oxide/metabolism
KW - Propanolamines/pharmacology
KW - Rats
KW - Rats, Inbred SHR
KW - Rats, Inbred WKY
KW - Serotonin/pharmacology
KW - Vascular Remodeling/drug effects
U2 - 10.1038/hr.2016.57
DO - 10.1038/hr.2016.57
M3 - SCORING: Journal article
C2 - 27250567
VL - 39
SP - 692
EP - 700
JO - HYPERTENS RES
JF - HYPERTENS RES
SN - 0916-9636
IS - 10
ER -
