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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 β adrenergic receptor-blocking agent reported to increase NO production and stimulate [β.sub.3] 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 [β.sub.3] adrenergic receptor immunoreactivity in pulmonary arteries and airways and that nebivolol has pulmonary vasodilator activity. Studies with [β.sub.3] receptor agonists (mirabegron, BRL 37344) and antagonists suggest that [β.sub.3] receptor-mediated decreases in systemic arterial pressure occur independent of NO release. Our results suggest that nebivolol, a selective vasodilating [β.sub.1] receptor antagonist that stimulates [β.sub.3] adrenergic receptors and induces vasodilation by increasing NO production, may be beneficial in treating pulmonary hypertensive disorders. Key words: nebivolol, beta receptors, pulmonary hypertension, nitric oxide, monocrotaline, pulmonary vascular bed, vasodilator response, cardiac output. Resume : L'hypertension pulmonaire est une maladie rare qui, si elle n'est pas traitee, progresse et est fatale en moins de 3 a 4 ans. Le traitement habituel implique un groupe varie de medicaments qui ciblent le lit vasculaire pulmonaire. De plus, des strategies qui accroissent la formation d'oxyde nitrique (NO) exercent des effets benefiques chez les rongeurs et les patients. Le nebivolol, un agent bloquant selectif du recepteur [β.sub.1]-adrenergique, rapporte accroitre la production de NO et stimuler les recepteurs [β.sub.3], possede des proprietes vasodilatatrices, suggerant qu'il pourrait etre benefique dans le traitement de l'hypertension pulmonaire. L'etude presente a ete realisee afin de determiner si le nebivolol exercait un effet benefique sur l'hypertension pulmonaire induite par la monocrotaline (60 mg/kg) chez le rat. Les resultats montrent que le traitement au nebivolol (10 mg/kg, une ou deux fois par jour) attenue l'hypertension pulmonaire, reduit le risque d'hypertrophie ventriculaire droite et ameliore le remodelage arteriel pulmonaire dans l'hypertension pulmonaire induite par la monocrotaline. Cette etude demontre la presence du recepteur [β.sub.3]-adrenergique par immuno-marquage dans les arteres pulmonaires et les voies aeriennes, et l'activite du nebivolol comme vasodilatateur dans le poumon. Des etudes realisees avec des agonistes du recepteur [β.sub.3] (mirabegron, BRL 37344) et des antagonistes du meme recepteur suggerent que des diminutions de la pression arterielle systemique mediees par le recepteur [β.sub.3] surviennent de maniere independante de la liberation de NO. Les resultats des auteurs suggerent que le nebivolol, un antagoniste vasodilatateur du recepteur [β.sub.1] qui stimule les recepteurs [β.sub.3]-adrenergiques et induit la vasodilatation en augmentant la production de NO, pourrait etre benefique dans le traitement des maladies hypertensives pulmonaires. [Traduit par la Redaction] Mots-cles: nebivolol, recepteurs beta, hypertension pulmonaire, oxyde nitrique, monocrotaline, lit vasculaire pulmonaire, vasodilatation, debit cardiaque., Introduction Pulmonary hypertension is a rare, progressive, and ultimately fatal disorder with 5-year survival rates of approximately 60% (Farber et al. 2015; McLaughlin et al. 2009). However, patients with early [...]

The actions of hydrogen sulfide (H 2 S) on the heart and vasculature have been extensively reported. However, the mechanisms underlying the effects of H 2 S are unclear in the anesthetized rat. The objective of the present study was to investigate the effect of H 2 S on the electrocardiogram and examine the relationship between H 2 S-induced changes in heart rate (HR), mean arterial pressure (MAP), and respiratory function. Intravenous administration of the H 2 S donor Na 2 S in the anesthetized Sprague-Dawley rat decreased MAP and HR and produced changes in respiratory function. The administration of Na 2 S significantly increased the RR interval at some doses but had no effect on PR or corrected QT( n )-B intervals. In experiments where respiration was maintained with a mechanical ventilator, we observed that Na 2 S-induced decreases in MAP and HR were independent of respiration. In experiments where respiration was maintained by mechanical ventilation and HR was maintained by cardiac pacing, Na 2 S-induced changes in MAP were not significantly altered, whereas changes in HR were abolished. Coadministration of glybenclamide significantly increased MAP and HR responses at some doses, but methylene blue, diltiazem, and ivabradine had no significant effect compared with control. The decreases in MAP and HR in response to Na 2 S could be dissociated and were independent of changes in respiratory function, ATP-sensitive K + channels, methylene blue-sensitive mechanism involving L-type voltage-sensitive Ca 2+ channels, or hyperpolarization-activated cyclic nucleotide-gated channels. Cardiovascular responses observed in spontaneously hypertensive rats were more robust than those in Sprague-Dawley rats. NEW & NOTEWORTHY H 2 S is a gasotransmitter capable of producing a decrease in mean arterial pressure and heart rate. The hypotensive and bradycardic effects of H 2 S can be dissociated, as shown with cardiac pacing experiments. Responses were not blocked by diltiazem, ivabradine, methylene blue, or glybenclamide., (Copyright © 2017 the American Physiological Society.)