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Updated: Mar 21, 2026
The Left Pneumonectomy Combined with Monocrotaline or Sugen as a Model of Pulmonary Hypertension in Rats
Published on: March 8, 2019
Nebivolol has a beneficial effect in monocrotaline-induced pulmonary hypertension
Edward A Pankey1, Justin A Edward1, Kevin W Swan1
1a Department of Pharmacology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112-2699, USA.
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.
Insights
Nebivolol effectively treats pulmonary hypertension in rats by reducing right ventricular hypertrophy and improving pulmonary artery remodeling. This selective beta-1 receptor antagonist stimulates beta-3 receptors, offering a potential new therapy for pulmonary hypertension.
Area of Science:
- Cardiovascular Pharmacology
- Pulmonary Medicine
- Adrenergic Receptor Research
Background:
- Pulmonary hypertension is a progressive, fatal disorder requiring effective treatments.
- Current therapies target the pulmonary vascular bed, with nitric oxide (NO) pathways showing promise.
- Nebivolol, a beta-1 blocker, may benefit pulmonary hypertension due to its NO-enhancing and beta-3 stimulating properties.
Purpose of the Study:
- To investigate the efficacy of nebivolol in a rat model of monocrotaline-induced pulmonary hypertension.
- To determine if nebivolol attenuates pulmonary hypertension, right ventricular hypertrophy, and pulmonary artery remodeling.
- To explore the role of beta-3 adrenergic receptors in nebivolol's pulmonary effects.
Main Methods:
- Induction of pulmonary hypertension in rats using monocrotaline (60 mg/kg).
- Administration of nebivolol (10 mg/kg, once or twice daily) to treated rats.
- Assessment of pulmonary hypertension, right ventricular hypertrophy, pulmonary artery remodeling, and beta-3 adrenergic receptor presence.
Main Results:
- Nebivolol treatment significantly attenuated pulmonary hypertension.
- Nebivolol reduced right ventricular hypertrophy and improved pulmonary artery remodeling.
- Beta-3 adrenergic receptor immunoreactivity was confirmed in pulmonary arteries and airways, suggesting a role in nebivolol's action.
Conclusions:
- Nebivolol demonstrates significant therapeutic potential for pulmonary hypertension.
- The drug's mechanism involves beta-3 adrenergic receptor stimulation and nitric oxide production, leading to vasodilation.
- Nebivolol may offer a novel treatment strategy for pulmonary hypertensive disorders.
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