Relationship Between Potassium Ion Channels and Airways Defence Reflexes Influenced by Experimentally Induced Allergic Inflammation in Guinea Pigs

Previously, we declared important role of ATP-sensitive (K_ATP) and calcium-sensitive (BK_Ca) potassium ion channels in cough and other defence reflexes of the airways coupled with reactivity of airways smooth muscle (ASM) and suggested their potential use as antitussives and antiasthmatic drugs.

The aim of presented studies was prove whether openers of potassium ion channels, K_ATP - pinacidil and BK_Ca - NS 1619, inhibit the cough reflex and modulate the ASM reactivity in conditions of experimental allergic inflammation of the airways in guinea pigs and if their influence on airways defence reflexes is changed by developing airways inflammation. Presented studies were realized in 4 partial experimental procedures with unsensitized guinea pigs and animal on 7^th, 14^th and 21th day of sensitization. Allergic inflammation of airways was induced by repetitive exposure of guinea pigs to ovalbumine and the degree of allergic inflammation was determined by histological analysis of tracheal and pulmonary samples. The cough reflex was induced by 0, 3 M citric acid aerosol for 3 min interval in which total number of coughs was counted. ASM reactivity in vivo was expressed as values of specific airway resistance (R. V) calculated by Pennock.

The cough response on the citric acid was significantly increased on 7^th and 14^th days of sensitization. The experiments showed persistent cough suppressive effect of pinacidil almost similar to codeine. The antitussive activity of NS 1619 remained only on 7^th day of sensitization similar to its effect in group of unsensitized animals. Sensitization by ovalbumine gradually increased the values of R. V on bronchoprovoking agent citric acid. Pinacidil suppressed R. V values of both, unsensitized and sensitized animals, more significantly than salbutamol. In unsensitized guinea pigs, NS 1619 significantly reduced R. V values, but allergic inflammation attenuated its bronchodilatory activity on 7^th and 14^th days. Histological analysis of specimens showed increasing signs of allergic inflammation during sensitization procedure as well as significant proinflammatory effect of pinacidil and NS 1619. Introduction of non-selective K_ATP agonists in clinical practice is strongly limited due to proinflammatory effect, but K_ATP of ASM represents a rational therapeutic target for novel drugs - tissue selective agonists of K_ATP.