| Asthma is a chronic disease of the airway which is clinically characterized by airway obstruction, enhanced bronchial responsiveness to spasmogens (airway hyperreactivity), and airway inflammation . Among them, airway inflammation is a central issue in the pathogenesis of asthma. Inflammation occurs throughout the lungs, extending from proximal airways through to alveolar tissue. It is also clear from pathologic investigations that airway hyperreactivity and structural alterations exist in the asthmatic airway.Asthma is characterized by airway inflammation that manifests as reversible airflow limitation and airway hyperresponsiveness. The inflammatory response in asthma is tightly associated with airway hyperresponsiveness, a hallmark of asthma.Consequently, anti-inflammatory and relieve airway hyperresponsiveness therapies play a pivotal role in its management.The term airway remodeling in asthma refers to structural change that occur in conjunction with, or because of, chronic airway inflammation. It includes epithelial cell changes,subepithelial collagendeposition,composition of the extracellular matrix(ECM),in addition to smooth muscle hypertrophy and/or hyperplasia. Airway remodeling results in alterations in the airway epithelium, lamina propria, and submucosa, leading to thickening of the airway wall. Airway remodeling that is now considered an important characteristic of asthma. Hence,airway remodeling responses in asthma are now being considered as potential targets for therapeutic intervention.Asthma used to be thought of as an entirely reversible disorder. As a consequence, our therapeutic approach to asthma has focused on symptomatic control through the alleviation of bronchospasm and the reduction of airway inflammation. It is now known, however, that this optimistic picture of the natural history of asthma is not entirely complete.Although of Asthma would seem able to account for much,there are many questions to need to be settled urgently. As we knowenjt is clear there are two principal pathologic changes, airway hyperreactivity and airway remodeling.This conceptual evolution predicts that we will acquire an enhanced understanding of asthma pathogenesis.Therefore,we will utilize this new perspective to identify novel targets against asthma.KATP channels couple the intracellular energy state to membrane excitability and regulate a wide array of biologic activities. Potassium channel openers alter membrane potential through KATP channels leading to potassium efflux, membrane hyperpolarization,thereby dilating smooth muscle .In a recent research,people have found KATP exists in many tissues(heart,muscle,nerve,et al). It implies an important mode of KATP channel modulation. During the past years a new class of pharmacologic agents has emerged that act like ligands to increase the activity of KATP channels. This diverse group of compounds has been termed KATP channel openers (KATpCOs). The presence of KATP channels within the lung is clear.Iptkalim hydrochloride(Ipk) is a novel KATpCOs supported by pharmacological, biochemical and binding studie.The aim of this study was to determine whether KATpCOs are capable of relaxing bronchial smooth muscle or decrease airway remodeling. The results of this study may contribute to answering the question as to whether asthma would benefit from the use of KATpCOs, but also may help in the understanding of the mechanism. In this investigation, we conducted a controlled,pinacidil and corticosteroids group, studied to assess the effects of novel KATpCOs onairway responsiveness and remodeling .They were reported for the first time. This paper was divided into two partsPart 1.Effects of KATPCOs on airway hyperresponsiveness in guinea-pigs with asthmaObjective To investigate the antiasthmatic action of KATpCOs in guinea-pigs with asthma .Methods Thirty-six guinea-pigs were randomly assigned to six groups: (1) control group, (2) asthma group, ( 3 )pinacidil group; ( 4 )high dose...
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