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 vasodilator in vivo . In the present study we evaluated the effect of inhaled CO on guinea‐pig airway smooth muscle tone. The mechanisms involved were characterized by use of a cyclic GMP antagonist, Rp‐8Br‐cyclic GMPS, and a nitric oxide synthase inhibitor, l ‐NAME. 2 Anaesthetized, ventilated 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 μg kg −1 min −1 ) to increase total pulmonary resistance ( R L ). Subsequent exposure to 7, 15 or 30 breaths of CO (100%), resulted in a dose‐dependent inhibition of the bronchoconstriction. In the highest dose tested (30 breaths), CO inhibited 80% of the histamine‐induced increase in R L . 3 In separate experiments, animals receiving histamine infusions followed by 30 breaths of CO, were pretreated with Rp‐8Br‐cyclic GMPS (0.05 mg kg −1 ). This pretreatment abolished >60% of the CO‐induced reduction in R L , but it had no effect on the bronchodilator response induced by salbutamol. In another set of experiments animals were 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.British Journal of Pharmacology (1998) 124 , 1065–1068; doi: 10.1038/sj.bjp.0701878