2026-08-29T15:34:14Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/52152024-09-27T10:00:09Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Garcia-Alvarez, Ana
author
Pereda, Daniel
author
Garcia-Lunar, Ines
author
Sanz-Rosa, David
author
Fernandez-Jimenez, Rodrigo
author
Garcia-Prieto, Jaime
author
Nuno-Ayala, Mario
author
Sierra, Federico
author
Santiago, Evelyn
author
Sandoval, Elena
author
Campelos, Paula
author
Aguero, Jaume
author
Pizarro, Gonzalo
author
Peinado, Victor I.
author
Fernandez-Friera, Leticia
author
Garcia-Ruiz, Jose M
author
Barberá, Joan Albert
author
Castella, Manuel
author
Sabaté, Manel
author
Fuster, Valentin
author
Ibáñez, Borja
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Instituto de Salud Carlos III
funder
Fundación Jesús Serra
funder
Ministerio de Economía y Competitividad (España)
funder
Fundación ProCNIC
2017-10-30T13:15:42Z
2017-10-30T13:15:42Z
2016
Basic Res Cardiol. 2016; 111(4):49
10.1007/s00395-016-0567-0
1435-1803
0300-8428
Basic Research in Cardiology
27328822
http://hdl.handle.net/20.500.12105/5215
Beta-3 adrenergic receptor (beta 3AR) agonists have been shown to produce vasodilation and prevention of ventricular remodeling in different conditions. Given that these biological functions are critical in pulmonary hypertension (PH), we aimed to demonstrate a beneficial effect of beta 3AR agonists in PH. An experimental study in pigs (n = 34) with chronic PH created by pulmonary vein banding was designed to evaluate the acute hemodynamic effect and the long-term effect of beta 3AR agonists on hemodynamics, vascular remodeling and RV performance in chronic PH. Ex vivo human experiments were performed to explore the expression of beta 3AR mRNA and the vasodilator response of beta 3AR agonists in pulmonary arteries. Single intravenous administration of the beta 3AR agonist BRL37344 produced a significant acute reduction in PVR, and two-weeks treatment with two different beta 3AR selective agonists, intravenous BRL37344 or oral mirabegron, resulted in a significant reduction in PVR (median of -2.0 Wood units/m(2) for BRL37344 vs. + 1.5 for vehicle, p = 0.04; and -1.8 Wood units/m(2) for mirabegron vs. + 1.6 for vehicle, p = 0.002) associated with a significant improvement in magnetic resonance-measured RV performance. Histological markers of pulmonary vascular proliferation (p27 and Ki67) were significantly attenuated in beta 3AR agonists-treated pigs. beta 3AR was expressed in human pulmonary arteries and beta 3AR agonists produced vasodilatation. beta 3AR agonists produced a significant reduction in PVR and improved RV performance in experimental PH, emerging as a potential novel approach for treating patients with chronic PH.
eng
Beta-3 adrenergic receptor
Pulmonary hypertension
Therapy
Pulmonary vascular resistance
NITRIC-OXIDE SYNTHASE
SMOOTH-MUSCLE-CELLS
BETA(3)-ADRENOCEPTOR AGONIST
OVERACTIVE BLADDER
ENDOTHELIAL DYSFUNCTION
HEART-TRANSPLANTATION
MAGNETIC-RESONANCE
ARTERY
MIRABEGRON
STIMULATION
Beta-3 adrenergic agonists reduce pulmonary vascular resistance and improve right ventricular performance in a porcine model of chronic pulmonary hypertension
journal article
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Beta-3AdrenergicAgonistsReduce_2016
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Beta-3AdrenergicAgonistsReduce_2016.txt