NO does not mediate inhibitory neural responses in sheep airway and bronchial vascular smooth muscle

Abstract

Endogenous nitric oxide (NO) influences acetylcholine-induced bronchovascular dilation in sheep and is a mediator of the airway smooth muscle inhibitory nonadrenergic, noncholinergic neural response in several species. This study was designed to determine the importance of NO as a neurally derived modulator of ovine airway and bronchial vascular smooth muscle. We measured the response of pulmonary resistance (Rl) and bronchial blood flow (Q˙br) to vagal stimulation in 14 anesthetized, ventilated, open-chest sheep during the following conditions: 1) control; 2) infusion of the α-agonist phenylephrine to reduce baseline Q˙br by the same amount as would be produced by infusion of N ω-nitro-l-arginine (l-NNA), a NO synthase inhibitor; 3) infusion ofl-NNA (10−2 M); and 4) after administration of atropine (1.5 mg/kg). The results showed that vagal stimulation produced an increase in Rl andQ˙br in periods 1, 2, and 3( P < 0.01) that was not affected byl-NNA. After atropine was administered, there was no increase inQ˙br or Rl. In vitro experiments on trachealis smooth muscle contracted with carbachol showed no effect ofl-NNA on neural relaxation but showed a complete blockade with propranolol ( P < 0.01). In conclusion, the vagally induced airway smooth muscle contraction and bronchial vascular dilation are not influenced by NO, and the sheep’s trachealis muscle, unlike that in several other species, does not have inhibitory nonadrenergic, noncholinergic innervation.