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 (Qbr) and pulmonary resistance (RL). In six sheep we measured the response of Qbr and RL to the dose of ACh required to produce 50% of the maximal increase in Qbr at baseline during infusion of the NO synthase inhibitor NG-nitro-L-arginine (L-NNA; 10(-2) M). Infusion of L-NNA decreased both the baseline Qbr (28 +/- 13 to 8 +/- 2 ml/min, P < 0.01) and the change in Qbr (delta Qbr) 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 Qbr (22 +/- 6 to 10 +/- 3 ml/min, P < 0.05) but not delta Qbr (62 +/- 13 to 66 +/- 21 ml/min, not significant). Infusion of L-NNA in these sheep decreased the baseline Qbr to a similar extent (11 +/- 5 ml/min) and also decreased delta Qbr (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.
Sasaki
F
F
University of British Columbia, Pulmonary Research Laboratory, St. Paul's Hospital, Vancouver, Canada.
Paré
P
P
Ernest
D
D
Bai
T
T
Verburgt
L
L
March
R
R
Baile
E
E
D000109:Acetylcholine / Q000494:pharmacology*; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001095:Arachidonic Acids / Q000652:urine; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001980:Bronchi / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D001993:Bronchodilator Agents / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D019335:Nitroarginine; D010656:Phenylephrine / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D012756:Sheep; D014665:Vasodilator Agents / Q000494:pharmacology*
D001095:Arachidonic Acids; D001993:Bronchodilator Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D000109:Acetylcholine