Airways Smooth Muscle
Airways Smooth Muscle

Author: David Raeburn

Publisher: Birkhauser

Published: 1996

Total Pages: 300

ISBN-13:

DOWNLOAD EBOOK

For researchers using animals to investigate human asthma, explains physiological and pharmacological process in the lung in vivo, and reviews the animal models available for studying the bronchospasm and inflammation associated with human asthma. Also discusses such methodological aspects as administering drugs to animal airways and the mechanics of assessing lung function. Also considers the use of genetically altered animals as research models. The sixth volume in the Airways Smooth Muscle sub- series. Annotation copyright by Book News, Inc., Portland, OR

Airways Smooth Muscle: Development, and Regulation of Contractility
Airways Smooth Muscle: Development, and Regulation of Contractility

Author: David Raeburn

Publisher: Birkhäuser

Published: 2013-03-08

Total Pages: 424

ISBN-13: 3034874081

DOWNLOAD EBOOK

Most studies on autonomic innervation of smooth muscle have focused on the short-term mechanisms involved in neurotransmission in physiological and pathophysiological conditions. However recent obser vations of the long-term plasticity of this system, i. e. its capacity for regeneration and for compensatory change in pattern of innervation and expression of cotransmitters and receptors in ageing, following surgery, trauma or in disease, have indicated that an understanding of the mechanisms involved could influence the design of therapeutic regimes. There is increasing evidence for long-term communication between nerves and smooth muscle cells during development and throughout adult life. To date, the trophic interactions between nerves and airway musculature have attracted little interest, consequently, much of the information presented here is drawn from studies using other smooth muscles. However, the questions posed about trophic interactions dur ing development apply as much to airways smooth muscle neuroeffector systems as to other autonomic neuroeffector systems. These are: i) How do developing nerve fibres know where to go and how do they reach their target sites? ii) What determines the density and pattern of inner vation at reaching the effector? iii) How do the nerves survive and maintain their position once established? iv) What factors influence neurochemical differentiation such that genetically multipotential neu rones are triggered to synthesize one or combinations of neurotransmit ters? v) What influence do nerves have on the structure, function and receptor expression of their effector cells? vi) How do diseases interrupt these processes? - see [1].

Advancing an Integrated Structure-function Relationship Between Airway Smooth Muscle, Airway Walls, and Airway Hyperreactivity
Advancing an Integrated Structure-function Relationship Between Airway Smooth Muscle, Airway Walls, and Airway Hyperreactivity

Author: Derek Anthony Affonce

Publisher:

Published: 2008

Total Pages: 324

ISBN-13:

DOWNLOAD EBOOK

Abstract: Asthma is characterized by thickening of the airway wall, inflammation, and airway hyperreactivity (AHR). One way remodeling and inflammation might lead to AHR is to promote reduced length cycling of the airway smooth muscle (ASM) which facilitates a transition of the ASM to a stiffer more contractile state. Interestingly, some non-asthmatic subjects such as spinal cord injury (SCI) patients have also been shown to have AHR. While SCI subjects would not be expected to have airway wall thickening or inflammation, they do not breathe as deeply and have a chronically reduced lung volume. The overall goal of this dissertation is to advance new insights on how the integrated airway system leads to AHR in asthmatics and non-asthmatics. We examined the problem at three levels: isolated ASM, single airways, and whole lung. At the level of isolated ASM strips we tested the effect of breathing on ASM reactivity using a "virtual loading" system. We found that (1) airway reactivity varies inversely with amplitude of tidal breathing (2) decreasing resting lung volume increased ASM reactivity in healthy but not "asthmatic" strips, and (3) sighs were bronchodilatory in the healthy but not "asthmatic" ASM strips. At the level of the individual airway we advanced a computational model of airway constriction. It was found increasing the force that ASM can generate, or reducing the resting load against which the ASM must constrict; may result in a generalized airway bi-stability. This bi-stability can be used to explain both AHR and airway hypersensitivity seen in asthmatics. Finally at the whole lung level we studied subjects with SCI to quantify their lung mechanics, ability to dilate their airways, and airway reactivity. It was found that subjects with SCI had decreased airway caliber and an inability to dilate their airways. The likely cause of both was reduced lung volumes resulting from their injury. We also found that subjects with high levels of SCI exhibit AHR and the degree of reactivity is dependent on resting lung volume. These three findings illustrate the key roles that stretch and resting lung volume have on airway reactivity.

Airway Smooth Muscle in Health and Disease
Airway Smooth Muscle in Health and Disease

Author: R.F. Coburn

Publisher: Springer Science & Business Media

Published: 2012-12-06

Total Pages: 325

ISBN-13: 1461307791

DOWNLOAD EBOOK

I organized this book because there is a need to put together in book form recent advances in our knowledge of how airway smooth muscle:works in health and in disease. After a period when it seemed that progress was very slow, there has been in the past few years an incredibly rapid gathering of knowledge in this area. In particular, our understanding has improved regarding the cascades of events that follow the initial binding of agonist to plasma membrane receptors and that lead to the cross-bridge movements that determine contraction. This advance in our knowledge was stimulated by use of single-and whole-cell channel recordings of plasma membrane currents and by description of the l3-receptor-GTP-binding protein-adenylate cyclase-cAMP coupling system, which serves as a model for other coupling mechanisms. The discovery of the receptor-activated inositol phospholipid transduction system has greatly stimulated research and led to advances in our understanding of mechanisms involved in smooth muscle con traction. Major advances were also triggered by the development of indicators for measuring free cytosolic calcium concentration and starting the unraveling of 2 the events involved in Ca + -dependent activation of contractile proteins. Al though most of the studies that led to our current understanding of these areas were performed on nonairway smooth muscle, these studies usually add to our understanding of airway smooth muscle, and there is an enlarging body of data that have been obtained on airway smooth muscle.

Role of Sarcoendoplasmic Reticulum Calcium ATPase Pump in Airway Smooth Muscle Function
Role of Sarcoendoplasmic Reticulum Calcium ATPase Pump in Airway Smooth Muscle Function

Author: Oluwaseun O Ojo

Publisher:

Published: 2011

Total Pages: 398

ISBN-13:

DOWNLOAD EBOOK

Asthma is a chronic inflammatory disease of the airway with hallmarks of remodelling, inflammation, hyper-responsiveness and bronchonstricition. All of these implicate airway smooth muscle (ASM) and alterations in ASM calcium homeostasis. We have found that the latter is mediated through diminished SERCA-2 expression, which correlates with disease severity. I investigated the role of SERCA-2 knock-down on ASM function using siRNA in ASM cells from healthy volunteers, and studied responses implicated in airway remodelling and inflammation. Calcium transients in healthy ASM following SERCA-2 knock-down resembled those from asthmatic ASM. Likewise, ASM proliferation in response to FBS and PDGF-[beta][beta], estimated using 3H-thymidine incorporation, was increased following SERCA-2 knock-down, similar to untreated ASM cells from asthmatics. SERCA-2 knock-down in both healthy and asthmatic ASM cells also elicited an increase in eotaxin-1 production in both untreated and IL-13 treated ASM cells. Collectively these data strongly suggest a key role for reduced SERCA-2 expression in the altered function and phenotype of ASM from asthmatics. To identify the cause of the diminished expression of SERCA-2 in asthma, I investigated the effect of asthma-associated mediators (cytokines and therapy) on SERCA-2 expression in healthy ASM cells, and observed decreased SERCA-2 expression following treatment with IL-13 and transforming growth factor- [beta](TGF[beta]); the later caused a reduction in expression that was sustained up to 14 days after removal of TGF[beta] following an initial 24 and 72 hrs exposure. Similarly, the long acting [beta]2 adrenoreceptor agonist formoterol also caused reduced expression of SERCA-2, and this was prevented by [beta]2 antagonists (ICI-118551) and inhibition of ERK signalling.