Effects of pinacidil on guinea-pig airway smooth muscle contracted by asthma mediators

Pinacidil is a new antihypertensive, direct vasodilator drug which has been classified as a K+ channel opener. The present study demonstrated a concentration-dependent relaxant activity of pinacidil in guinea-pig tracheal preparations. The potency and efficacy of pinacidil depended on the agent used to induce tracheal tone. Tracheal preparations with spontaneous tone or precontracted by different asthma mediators were completely relaxed by pinacidil. A high potency was found in spontaneously contracted preparations (EC50 = 7.8 x 10(-7) M). The EC50 values ranged from 2.3 to 5.4 x 10(-6) M in histamine-, PGF2 alpha- or LTC4-contracted preparations. When tone was induced by carbachol, the EC50 was 2.1 x 10(-5) M. In contrast, pinacidil produced incomplete relaxation and had a low potency in preparations contracted by 30 or 124 mM K+ Krebs solutions. This effect profile differed from that seen with beta 2-receptor agonists, xanthines and Ca2+ antagonists in guinea-pig trachealis and seems compatible with K+ channel opening as a primary mode of relaxation for pinacidil in airway smooth muscle.