title: Nebivolol has a beneficial effect in monocrotaline-induced pulmonary hypertension.
abstract: Pulmonary hypertension is a rare disorder that, without treatment, is progressive and fatal within 3-4 years. Current treatment involves a diverse group of drugs that target the pulmonary vascular bed. In addition, strategies that increase nitric oxide (NO) formation have a beneficial effect in rodents and patients. Nebivolol, a selective β1 adrenergic receptor-blocking agent reported to increase NO production and stimulate β3 receptors, has vasodilator properties suggesting that it may be beneficial in the treatment of pulmonary hypertension. The present study was undertaken to determine whether nebivolol has a beneficial effect in monocrotaline-induced (60 mg/kg) pulmonary hypertension in the rat. These results show that nebivolol treatment (10 mg/kg, once or twice daily) attenuates pulmonary hypertension, reduces right ventricular hypertrophy, and improves pulmonary artery remodeling in monocrotaline-induced pulmonary hypertension. This study demonstrates the presence of β3 adrenergic receptor immunoreactivity in pulmonary arteries and airways and that nebivolol has pulmonary vasodilator activity. Studies with β3 receptor agonists (mirabegron, BRL 37344) and antagonists suggest that β3 receptor-mediated decreases in systemic arterial pressure occur independent of NO release. Our results suggest that nebivolol, a selective vasodilating β1 receptor antagonist that stimulates β3 adrenergic receptors and induces vasodilation by increasing NO production, may be beneficial in treating pulmonary hypertensive disorders.
authors.affiliation: a Department of Pharmacology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112-2699, USA.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Pankey
authors.affiliation: a Department of Pharmacology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112-2699, USA.
authors.forename: Justin A
authors.initials: JA
authors.lastname: Edward
authors.affiliation: a Department of Pharmacology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112-2699, USA.
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Swan
authors.affiliation: b Department of Physiology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112-2699, USA.
authors.forename: Camille R T
authors.initials: CR
authors.lastname: Bourgeois
authors.affiliation: a Department of Pharmacology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112-2699, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Bartow
authors.affiliation: a Department of Pharmacology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112-2699, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Yoo
authors.affiliation: a Department of Pharmacology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112-2699, USA.
authors.forename: Taylor A
authors.initials: TA
authors.lastname: Peak
authors.affiliation: a Department of Pharmacology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112-2699, USA.
authors.forename: Bryant M
authors.initials: BM
authors.lastname: Song
authors.affiliation: a Department of Pharmacology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112-2699, USA.
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Chan
authors.affiliation: a Department of Pharmacology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112-2699, USA.
authors.forename: Subramanyam N
authors.initials: SN
authors.lastname: Murthy
authors.affiliation: b Department of Physiology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112-2699, USA.
authors.forename: Minolfa C
authors.initials: MC
authors.lastname: Prieto
authors.affiliation: c Department of Internal Medicine, Division of Cardiology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112-2699, USA.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Giles
authors.affiliation: a Department of Pharmacology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112-2699, USA.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Kadowitz
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology; D006976:Hypertension, Pulmonary / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D016686:Monocrotaline / Q000633:toxicity*; D000068577:Nebivolol / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D014665:Vasodilator Agents; D000068577:Nebivolol; D016686:Monocrotaline
keywords: beta receptors; cardiac output; débit cardiaque; hypertension pulmonaire; lit vasculaire pulmonaire; monocrotaline; nebivolol; nitric oxide; nébivolol; oxyde nitrique; pulmonary hypertension; pulmonary vascular bed; récepteurs bêta; vasodilatation; vasodilator response