Endogenous nitric oxide influences acetylcholine-induced bronchovascular dilation in sheep

To test whether endogenous endothelial nitric oxide (NO) influences baseline bronchial vascular tone and mediates acetylcholine (ACh)-induced bronchial vascular dilation and/or modulates bronchoconstriction in ovine airways, we studied anesthetized ventilated open-chest sheep and measured bronchial blood flow (Q̇br) and pulmonary resistance (RL). In six sheep we measured the response of Q̇br and RL to the dose of ACh required to produce 50% of the maximal increase in Q̇br at baseline during infusion of the NO synthase inhibitor N(G)-nitro-L-arginine (L-NNA; 10^-2M). Infusion of L-NNA decreased both the baseline Q̇br (28 ± 13 to 8 ± 2 ml/min, P < 0.01) and the change in Q̇br (ΔQ̇br) from the baseline value (84 ± 42 to 33 ± 18 ml/min, P < 0.05). There was no difference in baseline RL or in the response of RL to ACh at any time. In another six sheep phenylephrine (5 x 10^-6 to 5 x 10^-7 M) decreased baseline Q̇br (22 ± 6 to 10 ± 3 ml/min, P < 0.05) but not ΔQ̇br (62 ± 13 to 66 ± 21 ml/min, not significant). Infusion of L-NNA in these sheep decreased the baseline Q̇br to a similar extent (11 ± 5 ml/min) and also decreased ΔQ̇br (42 ± 16 ml/min, P < 0.05). We conclude that endogenous endothelial NO influences baseline vascular tone and ACh- induced vasodilation of the ovine bronchial vasculature but has no effect on baseline RL or ACh-induced bronchoconstriction.