Effects of neuraminidase on equine isolated bronchi

Abstract

A c c e p t e d m a n u s c r i p t AbstractIt has been demonstrated in mammals that the airway hyperresponsiveness which accompanies viral infections is the result of increased reflex bronchoconstriction due to inhibition of muscarinic prejunctional receptors, which belong to M2 subtypes. Multiple mechanisms account for virus-induced M2 receptor dysfunction. Viral neuraminidase may deglycosylate the M2 receptor, decreasing acetylcholine affinity. Equine influenza remains a common viral respiratory disease of horses worldwide, which results in loss to the equine industry, by decreasing performance, convalescence time and loss of peak performance due to chronic sequelae, such as airway hyperresponsiveness. The purpose of this study was to evaluate the effect of neuraminidase on equine isolated bronchi, assessed in equine bronchial smooth muscle rings, derived from five healthy equine male lungs. A pretreatment with vehicle did not modify contraction induced by EFS at each frequency tested. A pretreatment with pilocarpine (1 to 100 μM) significantly reduced, while methoctramine (1 to 100 μM) significantly increased contraction induced by EFS. Finally neuraminidase (0.5 Ul) significantly increased contraction induced by EFS. These results suggest that airway hyperresponsiveness that follows a viral influenza infection might be related to a dysfunction of muscarinic prejunctional receptors.

Pharmacological characterization of the interaction between aclidinium bromide and formoterol fumarate on human isolated bronchi

“…Although the response of isolated human ASM may not always be identical to that elicited in vivo, isolated airway preparations provide a suitable, convenient, and reproducible biological model for the evaluation of drug effects on ASM independent from the potential systemic influences found in vivo (Endoh and Hori, 2006;Iglarz et al, 2008). In particular, the configuration of the smooth muscle bundles is largely preserved in human isolated bronchi and therefore the bronchial contraction is directly related to airway narrowing Cazzola et al, 2011Cazzola et al, , 2012Hewson et al, 2012;Hulsmann and de Jongste, 1993;Matera et al, 2005Matera et al, , 2008Matera et al, , 2009Matera et al, , 2011aMatera et al, , 2011bRogliani et al, 2013).…”

Combining long‐acting bronchodilators with different mechanisms of action: A pharmacological approach to optimize bronchodilation of equine airways

“…In any case, since bronchial desensitization may be mediated by the activation of nonmyelinated C‐fibers and release of non‐neurogenic acetylcholine, the impact of a combination of tiotropium bromide and olodaterol on the contractile response elicited by EFS 3 Hz suggests that ultra‐LABA/LAMA combinations may have a role in preserving the physiological bronchial tone necessary to protect equine airways from the insult of external airborne agents. In this regard, severe asthmatic horses may benefit from preventive treatment with dual bronchodilation therapy that may support the pulmonary function in those horses that are at risk of bronchoconstriction, such as those having a viral influenza infection or undergoing sedation (Calzetta, Soggiu, et al., ; Matera et al., ).…”

“…Vagal firing largely determines the equine bronchial tone (Matera et al, 2002), and transmural stimulation of isolated airways activates vagal postganglionic fibers (Matera et al, 2008;Olszewski et al, 1999). Several neurotransmitters are released by transmural stimulation, the most representative is acetylcholine released by myelinated fibers, whereas nonmyelinated fibers mainly sustain neurogenic airway inflammation (Belvisi, 2002;Calzetta, Luongo, et al, 2015;Yu, Wang, & Robinson, 1993).…”

“…and Matera et al. have previously demonstrated that it is tetrodotoxin sensitive (Matera, Calzetta, Sanduzzi, Page, & Cazzola, ; Olszewski, Robinson, Zhu, Zhang, & Tithof, ).…”

Pharmacological interaction between LABAs and LAMAs in the airways: optimizing synergy

“…Although the response of human isolated ASM strictly resembles that elicited in vivo Cazzola et al, 2011Cazzola et al, , 2012Matera et al, 2009Matera et al, , 2011aMatera et al, ,b 2005Matera et al, , 2008Rogliani et al, 2013), results obtained from ex vivo studies need to be confirmed in clinical trials.…”