Abstract
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.
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 (RL). 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 RL.
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 RL, 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 RL.
The present findings indicate that CO causes bronchodilatation in vivo via cyclic GMP.
Keywords: Carbon monoxide, Rp-8Br-cyclic GMPS, airway, in vivo pharmacology, trachea, lung, dilatation
Full Text
The Full Text of this article is available as a PDF (448.6 KB).