INVOLVEMENT OF K-INTESTINAL-PEPTIDE AND ATRIAL-NATRIURETIC-PEPTIDE INISOLATED GUINEA-PIG TRACHEA( CHANNELS IN THE RELAXANT EFFECT OF VASOACTIVE)

The possible contribution of K+ channel activation to airway smooth mu scle relaxation induced by vasoactive intestinal peptide (VIP) and atr ial natriuretic peptide (ANP) was investigated in isolated guinea-pig trachea. Concentration-relaxation (CR) curves were assessed in prepara tions precontracted by 30 mM K+, 124 mM K+ or histamine either alone o r in the presence of a K+ channel blocker: iberiotoxin (IbTX), glipizi de, tetraethylammonium (TEA) or Ba2+. VIP completely relaxed contracti ons induced by histamine but had a lower effectiveness against those i nduced by 30 mM K+ and 124 mM K+. IbTX and TEA shifted the CR curve fo r VIP 5 and 14 times to the right, respectively. Glipizide and Ba2+ di d not significantly antagonize the action of VIP. ANP relaxed contract ions induced by histamine and 30 mM K+ but failed to relax those elici ted by 124 mM K+. IbTX and TEA shifted the CR curve for ANP 8 and 46 t imes to the right, respectively. Glipizide and Ba2+ suppressed the max imal effect produced by ANP, and glipizide also shifted the CR curve t o the left. The K+ channel opener levcromakalim relaxed tracheal contr actions induced by histamine and 30 mM K+ but not those induced by 124 mM K+. Glipizide caused a 5-fold rightward shift of the CR curve for levcromakalim whereas IbTX shifted the curve to the left and increased the maximal relaxant effect. The Ca2+ channel blocker isradipine comp letely relaxed contractions induced by 30 mM K+ and 124 mM K+ but only partially relaxed those contracted by histamine. All four K+ channel blockers increased the maximal relaxant effect and shifted the CR curv e for isradipine to the left. The results suggest that airway smooth m uscle relaxation produced by VIP and ANP involves activation of large- conductance Ca2+-activated K+ channels (BKCa) and further that ANP may possibly activate other types of K+ channels additional to BKCa.