Possible role of cAMP, cGMP and [Ca2+]i during NANC relaxation in the cat airway smooth muscle.

To investigate the possible role of cyclic nucleotides and [Ca2+]i in non-adrenergic non-cholinergic (NANC) relaxations evoked by electrical field stimulation (EFS) in the cat airway, we studied the effects of specific phosphodiesterase (PDE) type IV or V inhibitors on the biphasic-NANC relaxations, the correlation between NANC relaxation and changes 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 to 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 (> 3 x 10(-7) M), a specific PDE type V inhibitor, preferentially enhanced the amplitude of the first component of the NANC relaxations. However, rolipram (> 3 x 10(-7) M) enhanced both the first and second component of the NANC relaxation 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 accumulation of [cAMP]i and amplitude of NANC relaxation evoked by EFS. However, zaprinast did not affect the amplitude of NANC relaxation although it significantly increased the levels of [cGMP]i. Nomega-Nitro-L-arginine methylester (L-NAME; 10(-5) M) completely suppressed the accumulation of [cGMP]i but only partly suppressed the NANC relaxation evoked by EFS. In contrast, EFS significantly enhanced [cAMP]i in the presence of L-NAME. During NANC relaxation, time-dependent decrease in [Ca2+]i occurred, which was partly suppressed by L-NAME. These results indicate that NANC relaxation is associated with concomitant accumulation in both [cAMP]i and [cGMP]i, and decrease in [Ca2+]i. However, the timing of the action of [cGMP]i and [cAMP]i in NANC relaxations differs in the central and peripheral airway.