Mechanisms of airway smooth muscle relaxation during maturation

2005 ◽  
Vol 83 (10) ◽  
pp. 833-840 ◽  
Author(s):  
Lu Wang ◽  
Thomas M Murphy ◽  
Pasquale Chitano
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Muscle Relaxation ◽  
Electrical Field Stimulation ◽  
Airway Responsiveness ◽  
Smooth Muscle Relaxation ◽  
Asthma Prevalence ◽  
Spontaneous Relaxation

Greater airway responsiveness in healthy juveniles is considered a factor in the higher asthma prevalence at a young age compared with adults. We have developed a guinea pig maturational model that utilizes tracheal strips from 1-week-, 3-week-, and 3-month-old guinea pigs to study the role of airway smooth muscle (ASM) in juvenile airway hyperresponsiveness. Because a reduced ability of ASM to spontaneously relax may contribute to airway hyperresponsiveness by maintaining bronchospasm and thus high airway resistance, we have employed this model to study ASM spontaneous relaxation during electrical field stimulation (EFS). Since relaxation during EFS had been neither described nor quantified during maturation, we developed new indices that allowed an appropriate comparison of the relaxing response from strips of different age animals. Using these indices we found that, whereas strips from adult animals relax to a level of tension similar to that found in the absence of stimulation, this ability to spontaneously relax is essentially absent in trachealis from infant animals. These results confirmed that maturation of ASM relaxation may play a role in juvenile airway hyperresponsiveness and that our maturational model is suitable to study the mechanisms regulating spontaneous relaxation in physiological conditions. We investigated the role of prostanoids in ASM relaxation and showed that cyclooxygenase inhibition increases relaxation in infant ASM to levels similar to adults. These results suggest that prostanoids regulate the ability of ASM to spontaneously relax, i.e., they reduce relaxation. We have produced preliminary data suggesting a maturational change in the level of prostanoids. Moreover, the possible action of acetylcholinesterase on maturation of ASM relaxation is discussed here on the basis of a preliminary study. We suggest that impairment of ASM relaxation likely contributes to increased airway responsiveness.Key words: acetylcholinesterase, airway responsiveness, asthma, ontogenesis, prostanoids.

scholarly journals Relaxation of guinea pig trachealis during electrical field stimulation increases with age

2002 ◽  
Vol 92 (5) ◽  
pp. 1835-1842 ◽  
Author(s):  
Pasquale Chitano ◽  
Carrie M. Cox ◽  
Thomas M. Murphy
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Time Course ◽  
Muscle Relaxation ◽  
Electrical Field Stimulation ◽  
Smooth Muscle Relaxation ◽  
Age Difference ◽  
Field Stimulation ◽  
Electrical Field

Our laboratory has previously shown that maturation of airway smooth muscle (ASM) contractility may play a role in the airway hyperresponsiveness displayed by juveniles of many species, including humans (Chitano P, Wang J, Cox CM, Stephens NL, and Murphy TM. J Appl Physiol 88: 1338–1345, 2000). ASM relaxation, which could also contribute to airway hyperresponsiveness, has neither been described nor quantified during maturation. Therefore, we studied ASM relaxation during and after electrical field stimulation (EFS) in tracheal strips from 1-wk-old, 3-wk-old, and 3-mo-old guinea pigs. Strips were stimulated (60 Hz, 18 V) at their optimal length for 15, 20, and 25 s, with and without the cyclooxygenase inhibitor indomethacin. To evaluate the role of the epithelium, deepithelialized strips from adult animals were also studied. New indexes were developed to quantify relaxation during EFS. We measured the time course of tension relaxation and its maximum rate (RTR) during the EFS, as well as the residual tension at the end of the EFS (TCTend). After EFS, we measured the maximum RTR and the time needed to reduce to half the TCTend. Relaxation during the EFS significantly increased with age. Indomethacin reduced this age difference by increasing relaxation in strips from younger animals. By contrast, removal of the epithelium in adult strips decreased relaxation. Relaxation after EFS decreased with age and was not affected by indomethacin. In adult strips, it was further reduced by epithelium removal. Our results show that during EFS 1) airway smooth muscle relaxation increases with age, 2) cyclooxygenase metabolites oppose relaxation in younger animals, and 3) epithelium removal inhibits relaxation. We suggest that a reduced ASM relaxing ability during stimulation may be involved in juvenile airway hyperresponsiveness.

Adrenomedullin insufficiency increases allergen-induced airway hyperresponsiveness in mice

2007 ◽  
Vol 102 (6) ◽  
pp. 2361-2368 ◽  
Author(s):  
Hiroshi Yamamoto ◽  
Takahide Nagase ◽  
Takayuki Shindo ◽  
Shinji Teramoto ◽  
Tomoko Aoki-Nagase ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Airway Responsiveness ◽  
Mutant Mice ◽  
Wild Type ◽  
T Helper 1 ◽  
Littermate Control

Adrenomedullin (ADM), a newly identified vasodilating peptide, is reported to be expressed in lungs and have a bronchodilating effect. We hypothesized whether ADM could be involved in the pathogenesis of bronchial asthma. We examined the role of ADM in airway responsiveness using heterozygous ADM-deficient mice ( AM+/−) and their littermate control ( AM+/+). Here, we show that airway responsiveness is enhanced in ADM mutant mice after sensitization and challenge with ovalbumin (OVA). The immunoreactive ADM level in the lung tissue after methacholine challenge was significantly greater in the wild-type mice than that in the mutant. However, the impairment of ADM gene function did not affect immunoglobulins (OVA-specific IgE and IgG1), T helper 1 and 2 cytokines, and leukotrenes. Thus the conventional mechanism of allergen-induced airway responsiveness is not relevant to this model. Furthermore, morphometric analysis revealed that eosinophilia and airway hypersecretion were similarly found in both the OVA-treated ADM mutant mice and the OVA-treated wild-type mice. On the other hand, the area of the airway smooth muscle layer of the OVA-treated mutant mice was significantly greater than that of the OVA-treated wild-type mice. These results suggest that ADM gene disruption may be associated with airway smooth muscle hyperplasia as well as enhanced airway hyperresponsiveness. ADM mutant mice might provide novel insights to study the pathophysiological role of ADM in vivo.

scholarly journals Role of L‐Citrulline/L‐Arginine Cycle in Hyperoxia‐Induced Decrease of Airway Smooth Muscle Relaxation

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Ramadan Sopi ◽  
Icko Gjorgoski ◽  
Mitko Mladenov ◽  
Azem Lajçi ◽  
Muharrem Jakupaj
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Muscle Relaxation ◽  
Smooth Muscle Relaxation

Airway smooth muscle relaxation induced by 5-HT2A receptors: Role of Na+/K+-ATPase pump and Ca2+-activated K+ channels

Life Sciences ◽  
2008 ◽  
Vol 83 (11-12) ◽  
pp. 438-446 ◽  
Author(s):  
Patricia Campos-Bedolla ◽  
Mario H. Vargas ◽  
Patricia Segura ◽  
Verónica Carbajal ◽  
Eduardo Calixto ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Muscle Relaxation ◽  
Smooth Muscle Relaxation ◽  
K Channels

Role of cGMP in relaxation of vascular and other smooth muscle

1989 ◽  
Vol 67 (4) ◽  
pp. 251-262 ◽  
Author(s):  
Kanji Nakatsu ◽  
Jack Diamond
Keyword(s):  
Smooth Muscle ◽  
Muscle Relaxation ◽  
Smooth Muscles ◽  
Phosphodiesterase Inhibitors ◽  
Current Evidence ◽  
Smooth Muscle Relaxation ◽  
Drug Induced ◽  
Intracellular Cgmp ◽  
Tissue Content

The hypothesis that the relaxant action of many drugs on vascular and other smooth muscle is mediated by increases in intracellular cGMP, the "cGMP hypothesis," is gaining wide acceptance. While much information supporting this idea can be found in the literature, there is also a significant amount of information indicating that an elevation in the tissue content of cGMP is by itself insufficient to cause smooth muscle relaxation. The literature is reviewed with reference to the criteria that need to be fulfilled to consider cGMP as the second messenger mediating relaxation of smooth muscle by a drug; i.e., activation of guanylate cyclase, elevation of tissue content of cGMP, potentiation by phosphodiesterase inhibitors, antagonism by inhibitors of cGMP synthesis, and production of relaxation by cGMP analogues. For each criterion, key observations supporting the hypothesis are considered, followed by examples of important observations not consistent with the hypothesis. It is concluded that in some smooth muscles, for example, rat myometrium and vas deferens, cGMP is not a mediator of drug-induced relaxation. In other smooth muscles, including vascular smooth muscle, cGMP appears to play an important role in the relaxation process; but current evidence suggests that other factors are also important and that the cGMP hypothesis may need to be modified.Key words: cGMP, vascular relaxation, smooth muscle relaxation, vasodilators.

EETs relax airway smooth muscle via an EpDHF effect: BKCa channel activation and hyperpolarization

2001 ◽  
Vol 280 (5) ◽  
pp. L965-L973 ◽  
Author(s):  
Catherine Benoit ◽  
Barbara Renaudon ◽  
Dany Salvail ◽  
Eric Rousseau
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Molecular Mechanisms ◽  
Muscle Tone ◽  
Muscle Relaxation ◽  
Smooth Muscle Relaxation ◽  
Epoxyeicosatrienoic Acids ◽  
Bkca Channel ◽  
Channel Activity ◽  
Cytochrome P 450

Epoxyeicosatrienoic acids (EETs) are produced from arachidonic acid via the cytochrome P-450 epoxygenase pathway. EETs are able to modulate smooth muscle tone by increasing K+ conductance, hence generating hyperpolarization of the tissues. However, the molecular mechanisms by which EETs induce smooth muscle relaxation are not fully understood. In the present study, the effects of EETs on airway smooth muscle (ASM) were investigated using three electrophysiological techniques. 8,9-EET and 14,15-EET induced concentration-dependent relaxations of the ASM precontracted with a muscarinc agonist (carbamylcholine chloride), and these relaxations were partly inhibited by 10 nM iberiotoxin (IbTX), a specific large-conductance Ca2+-activated K+ (BKCa) channel blocker. Moreover, 3 μM 8,9- or 14,15-EET induced hyperpolarizations of −12 ± 3.5 and −16 ± 3 mV, with EC50 values of 0.13 and 0.14 μM, respectively, which were either reversed or blocked on addition of 10 nM IbTX. These results indicate that BKCa channels are involved in hyperpolarization and participate in the relaxation of ASM. In addition, complementary experiments demonstrated that 8,9- and 14,15-EET activate reconstituted BKCa channels at low free Ca2+ concentrations without affecting their unitary conductance. These increases in channel activity were IbTX sensitive and correlated well with the IbTX-sensitive hyperpolarization and relaxation of ASM. Together these results support the view that, in ASM, the EETs act through an epithelium-derived hyperpolarizing factorlike effect.

scholarly journals Opsin 3–Gαs Promotes Airway Smooth Muscle Relaxation Modulated by G Protein Receptor Kinase 2

2021 ◽  
Vol 64 (1) ◽  
pp. 59-68
Author(s):  
Amy D. Wu ◽  
William Dan ◽  
Yi Zhang ◽  
Shruti Vemaraju ◽  
Brian A. Upton ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
G Protein ◽  
Airway Smooth Muscle ◽  
Muscle Relaxation ◽  
Smooth Muscle Relaxation ◽  
Receptor Kinase ◽  
Protein Receptor
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