NEBIVOLOL HAS A BENEFICIAL EFFECT IN MONOCROTALINE-INDUCED PULMONARY HYPERTENSION

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 if nebivolol has a beneficial effect in monocrotaline-induced (60mg/kg) pulmonary hypertension in the rat. These results show that nebivolol treatment (10 mg/kg qd/bid) 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 stimulates β3 adrenergic receptors and induces vasodilation by increasing NO production may be beneficial in treating pulmonary hypertensive disorders.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author