British journal of pharmacology
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The present study investigated whether the pathophysiological changes induced by burn and smoke inhalation are modulated by parenteral administration of Na(2)S, a H(2)S donor. ⋯ Parenteral administration of the H(2)S donor ameliorated the pulmonary pathophysiological changes associated with burn- and smoke-induced acute lung injury. Based on the effect of H(2)S observed in this clinically relevant model of disease, we propose that treatment with H(2)S or its donors may represent a potential therapeutic strategy in managing patients with acute lung injury.
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Increased airway smooth muscle (ASM) mass plays a critical role in chronic asthmatic airway remodelling. ASM cell hypertrophy and hyperplasia are likely to contribute to increased ASM mass and a variety of mitogens induce ASM proliferation in cell culture. Recent recognition of widespread vitamin D deficiency and identification of the vitamin D receptor on many cells has implicated vitamin D as a potential therapeutic target for many disorders including cancer, infection and asthma. ⋯ They also, perhaps surprisingly, show the glucocorticoid dexamethasone to potentiate mitogen-induced ASM proliferation. Their results begin to elucidate the molecular mechanism(s) utilized by calcitriol to inhibit cell proliferation and suggest hyperphosphorylation of retinoblastoma protein and activation of checkpoint kinase 1 (Chk1) as critical to this process. This study identifies inhibition of ASM proliferation as a cellular effect of vitamin D and supports the hypothesis that vitamin D is a potential treatment for airway remodelling in asthma.
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The transient receptor potential ankyrin receptor 1 (TRPA1) is a cation channel, co-expressed with the pro-tussive transient receptor potential vanilloid type 1 (TRPV1) channel in primary sensory neurons. TRPA1 is activated by a series of irritant exogenous and endogenous alpha,beta-unsaturated aldehydes which seem to play a role in airway diseases. We investigated whether TRPA1 agonists provoke cough in guinea pigs and whether TRPA1 antagonists inhibit this response. ⋯ A novel pro-tussive pathway involves the TRPA1 channel, expressed by capsaicin-sensitive airway sensory nerves and is activated by a series of exogenous (cigarette smoke) and endogenous irritants. These results suggest TRPA1 may be a novel target for anti-tussive medicines.
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Central 5-hydroxytryptamine (5-HT)-containing pathways utilizing 5-HT(7) receptors are known to be critical for the mediation of cardiovascular reflexes. The nucleus tractus solitarius (NTS) is a site involved in the integration of cardiovascular afferent information. The present experiments examined the involvement of the 5-HT(7) receptor in the processing of cardiovascular reflexes in the NTS. ⋯ Vagal afferent-evoked excitation of NTS neurones can be blocked by SB 258719, a selective 5-HT(7) antagonist. This observation further supports the involvement of 5-HT neurotransmission in NTS afferent processing.