POSSIBLE ROLE OF CAMP, CGMP AND [CA2-MUSCLE(](I) DURING NANC RELAXATION IN THE CAT AIRWAY SMOOTH)

To investigate the possible role of cyclic nucleotides and [Ca2+](i) i n non-adrenergic non-cholinergic (NANC) relaxations evoked by electric al field stimulation (EFS) in the cat airway, we studied the effects o f specific phosphodiesterase (PDE) type TV or V inhibitors on the biph asic-NANC relaxations, the correlation between NANC relaxation and cha nges in intracellular levels of cAMP and cGMP ([cAMP](i) and [cGMP](i) ), and measured changes in [Ca2+](i) during the NANC relaxation. EFS ( repetitive stimuli at 20 Hz, 1 or 4 ms pulse duration, 50 V) applied t o the bronchial smooth muscle during contraction induced by 5-HT (10(- 5) M) in the presence of atropine (10(-6) M) and guanethidine (10(-6) M) elicited biphasic NANC relaxations. Zaprinast (>3X10(-7) M), a spec ific PDE type V inhibitor, preferentially enhanced the amplitude of th e first component of the NANC relaxations. However, rolipram (> 3 X 10 (-7) M) enhanced both the first and second component of the NANC relax ation to a similar extent. In the trachea, EFS evoked monophasic NANC relaxation accompanied by a concomitant accumulation of [cAMP](i) and [cGMP](i). Pretreatment with rolipram (3 X 10(-6) M) enhanced the accu mulation of [cAMP](i) and amplitude of NANC relaxation evoked by EFS. However, zaprinast did not affect the amplitude of NANC relaxation alt hough it significantly increased the levels of [cGMP](i). N-omega-Nitr o-L-arginine methylester (L-NAME; 10(-5) M) completely suppressed the accumulation of [cGMP](i) but only partly suppressed the NANC relaxati on evoked by EFS. In contrast, EFS significantly enhanced [cAMP], in t he presence of L-NAME. During NANC relaxation, time-dependent decrease in [Ca2+](i) occurred, which was partly suppressed by L-NAME. These r esults indicate that NANC relaxation is associated with concomitant ac cumulation in both [cAMP](i) and [cGMP]i, and decrease in [Ca2+](i). H owever, the timing of the action of [cGMP](i) and [cAMP](i) in NANC re laxations differs in the central and peripheral airway. (C) 1998 Elsev ier Science B.V.