BRONCHODILATATION IN-VIVO BY CARBON-MONOXIDE, A CYCLIC-GMP RELATED MESSENGER

1 Recent studies suggest that gaseous carbon monoxide (CO) is involved in neurotransmission and that this molecule also is an important vaso dilator in vivo. In the present study we evaluated the effect of inhal ed CO on guinea-pig airway smooth muscle tone. The mechanisms involved were characterized by use of a cyclic GMP antagonist, Rp-8Br-cyclic G MPS, and a nitric oxide synthase inhibitor, L-NAME. 2 Anaesthetized, v entilated guinea-pigs were given a bolus injection of histamine (0.12 mg kg(-1), i.v.), followed by a continuous infusion of histamine (0.30 mu g kg(-1) min(-1)) to increase total pulmonary resistance (R-L). Su bsequent exposure to 7, 15 or 30 breaths of CO (100%), resulted in a d ose-dependent inhibition of the bronchoconstriction. In the highest do se tested (30 breaths), CO inhibited 80% of the histamine-induced incr ease in R-L. 3 In separate experiments, animals receiving histamine in fusions followed by 30 breaths of CO, were pretreated with Rp-8Br-cycl ic GMPS (0.05 mg kg(-1)). This pretreatment abolished >60% of the CO-i nduced reduction in R-L, but it had no effect on the bronchodilator re sponse induced by salbutamol. In another set of experiments animals we re pretreated with L-NAME (1.60 mg kg(-1)). In contrast to the Rp 8Br- cyclic GMPS pretreatment, the pretreatment with L-NAME did not affect the CO-induced reduction in R-L. 4 The present findings indicate that CO causes bronchodilatation in vivo via cyclic GMP.