Sildenafil decreases rat tracheal hyperresponsiveness to carbachol and changes canonical transient receptor potential gene expression after antigen challenge

Sousa, Carla Thais de; Brito, Teresinha Silva de; Lima, F. J. B.; Siqueira, Rodrigo José Bezerra de; Magalhães, Pedro J.C.; Lima, Aldo A. M.; Santos, Armênio Aguiar dos; Havt, Alexandre

doi:10.1590/s0100-879x2011007500056

Cited by 6 publications

(4 citation statements)

References 36 publications

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“…While gene expression of TRPC1 and TRPC6 decreased, TRPC5 increased and TRPC4 was refractory to the antigen challenge. Upregulation of TRPC1 expression was reported in rat trachea and proliferating airway smooth muscle cells, while TRPC1 downregulation diminished store‐depletion‐induced Ca 2+ influx and airway hyper‐responsiveness in the presence of inflammatory mediators . In mice challenged with OVA, downregulation of TRPC6 resulted in increased agonist‐induced contractility of tracheal rings, findings in line with the present results obtained with rat airways.…”

Section: Discussionsupporting

confidence: 91%

Inhibitory effects of a standardized extract ofJusticia pectoralisin an experimental rat model of airway hyper-responsiveness

Moura

Batista‐Lima

Brito

et al. 2017

Journal of Pharmacy and Pharmacology

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Section: Discussionsupporting

confidence: 91%

Inhibitory effects of a standardized extract ofJusticia pectoralisin an experimental rat model of airway hyper-responsiveness

Moura

Batista‐Lima

Brito

et al. 2017

Journal of Pharmacy and Pharmacology

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“…Transmembrane influx of Ca 2+ through store-operated Ca 2+ channels ("capacitative Ca 2+ entry") ( 28 , 29 ) can be also triggered under experimental conditions in preparations of rat trachea. This phenomenon can be activated in preparations maintained in Ca 2+ -free medium after treatment with thapsigargin (1 µM), a non-competitive inhibitor of sarcoplasmic/endoplasmic reticulum Ca 2+ ATPase ( 30 ).…”

Section: Resultsmentioning

confidence: 99%

β-Citronellol, an alcoholic monoterpene with inhibitory properties on the contractility of rat trachea

Vasconcelos

Ribeiro-Filho

Lucetti

et al. 2016

Braz J Med Biol Res

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β-Citronellol is an alcoholic monoterpene found in essential oils such Cymbopogon citratus (a plant with antihypertensive properties). β-Citronellol can act against pathogenic microorganisms that affect airways and, in virtue of the popular use of β-citronellol-enriched essential oils in aromatherapy, we assessed its pharmacologic effects on the contractility of rat trachea. Contractions of isolated tracheal rings were recorded isometrically through a force transducer connected to a data-acquisition device. β-Citronellol relaxed sustained contractions induced by acetylcholine or high extracellular potassium, but half-maximal inhibitory concentrations (IC50) for K+-elicited stimuli were smaller than those for cholinergic contractions. It also inhibited contractions induced by electrical field stimulation or sodium orthovanadate with pharmacologic potency equivalent to that seen against acetylcholine-induced contractions. When contractions were evoked by selective recruitment of Ca2+ from the extracellular medium, β-citronellol preferentially inhibited contractions that involved voltage-operated (but not receptor-operated) pathways. β-Citronellol (but not verapamil) inhibited contractions induced by restoration of external Ca2+ levels after depleting internal Ca2+ stores with the concomitant presence of thapsigargin and recurrent challenge with acetylcholine. Treatment of tracheal rings with L-NAME, indomethacin or tetraethylammonium did not change the relaxing effects of β-citronellol. Inhibition of transient receptor potential vanilloid subtype 1 (TRPV1) or transient receptor potential ankyrin 1 (TRPA1) receptors with selective antagonists caused no change in the effects of β-citronellol. In conclusion, β-citronellol exerted inhibitory effects on rat tracheal rings, with predominant effects on contractions that recruit Ca2+ inflow towards the cytosol by voltage-gated pathways, whereas it appears less active against contractions elicited by receptor-operated Ca2+ channels.

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“…Sousa et al showed that sildenafil relaxed carbachol contracted and OVA-sensitized rat airways in a concentration-dependent manner [33]. In guinea pigs, Toward et al showed that sildenafil treatment did not affect histamine-induced bronchoconstriction [34].…”

Section: Discussionmentioning

confidence: 99%

Phosphodiesterase V Inhibition Reduces Airway Responsiveness, but Does Not Improve the Beneficial Effect of Deep Inspiration

Pyrgos¹,

Togias

Brown³

2013

Respiration

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Background: Deep inspirations (DIs) can prevent (bronchoprotection; BP) and reverse (bronchodilation; BD) methacholine (Mch)-induced bronchoconstriction, but this effect is reduced or absent in people with asthma or airways hyperresponsiveness (AHR). The mechanisms of this defect are unknown. Objective: To indirectly examine the role of guanosine 3′,5′-cyclic monophosphate (cGMP) by testing the hypothesis that the phosphodiesterase (PDE) V inhibitor, sildenafil, would improve DI-induced BP in individuals with AHR. Methods: Thirty-two individuals were screened and 15 met all the inclusion/exclusion criteria (7 subjects with AHR and 8 healthy subjects). A single-dose Mch challenge inducing a 20% reduction in FEV₁ in the absence of DIs was first identified. Thereafter, every study participant had 4 pairs of visits, each pair testing DI-induced BP and BD against the single-dose Mch, with no drug, or pretreatment with 25, 50 and 100 mg of sildenafil, respectively, in consecutive order. Results: Sildenafil did not influence baseline lung function. However, in the absence of DIs, the drug caused a dose-dependent attenuation of the Mch-induced decrease in FEV₁ by 17% (median value; 25th percentile: 1, 75th percentile: 16), 35% (-3, 61) and 37% (13, 79) for the 25-, 50- and 100-mg doses, respectively (p = 0.0004). No differences between the two participant groups were found. There were no effects of sildenafil on DI-induced BP or BD. Conclusion: We infer from these results that the mechanism responsible for the defective ability of DIs to protect the airways from bronchoconstriction is unlikely to be due to dysregulation of cGMP. Of importance, a potential role for PDE V inhibition as a bronchoprotector treatment needs to be explored.

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Sildenafil decreases rat tracheal hyperresponsiveness to carbachol and changes canonical transient receptor potential gene expression after antigen challenge

Cited by 6 publications

References 36 publications

Inhibitory effects of a standardized extract ofJusticia pectoralisin an experimental rat model of airway hyper-responsiveness

Inhibitory effects of a standardized extract ofJusticia pectoralisin an experimental rat model of airway hyper-responsiveness

β-Citronellol, an alcoholic monoterpene with inhibitory properties on the contractility of rat trachea

Phosphodiesterase V Inhibition Reduces Airway Responsiveness, but Does Not Improve the Beneficial Effect of Deep Inspiration

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