Pharmacological studies on the NO-dependent and -independent NANC neurotransmitters in the human and cat airway.

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Neurally mediated relaxation of airway smooth muscle, in various animal species including man, is largely non-adrenergic, non-cholinergic (NANC). Although the neurotransmitter (s) responsible for the NANC relaxation in the airways have not been conclusively identified, vasoactive intestinal polypeptide (VIP) and nitric oxide (NO) have emerged as strong candidate for this role. The present study were carried out to examine whether and to what extent NO-related compounds and VIP mediate the NANC relaxation in cat and human airway. NANC relaxation evoked by EFS in the cat peripheral airway was biphasic, comprising an initial fast followed by a second slow component and L-NAME or L-NNA selectively abolished the first component without affecting the second one. C-PTIO,a newly synthesized NO scavenger, dose-dependently suppressed the initial component and at a concentration of 10^<-4>M almost halved the amplitude of NANC relaxation. Additional application of L-NAME further reduced the C-PTIO … More resistant NANC relaxation, thereby suggesting that the initial component of the NANC relaxation is due to NO free radial itself and NO-donors. The amplitude of the L-NAME insensitive NANC relaxation showed a fade phenomenon during the first 1 hr of stimulation at an interval of every 20min. Application of VIP (10-28) , a VIP antagonist, enhanced the rate of decrease in the amplitude of L-NAME-insensitive NANC relaxation. Zaprinast, a specific PDE tupe V inhibitor, preferentially enhanced the amplitude of the firstcomponent of the NANC relaxation, and enhanced the accumulation of [cGMP] i evoked by EFS.Rolipram, a specific PDE type IV inhibitor, enhanced both the first ad second components of the NANC relaxation to a similar extent, and enhanced the accumulator of [cAMP] i, thereby indicating that NANC relaxation is associated with concomitant accumulation in both [cAMP] i and [cGMP] i. Taken together, the present study have shown that at least NO free radical itself and NO donors such as nitrosocystine, and VIP are involved as neurotransmitters in the NANC relaxation in the airway. Less