The role of nitric oxide in the pathophysiology of bronchial asthma

Abstract

OBJECTIVE: To study in vitro the role of nitric oxide (NO), in the pathophysiology of asthma observing the effections of a NO-donor such as sodium nitroprusside, a calcium (Ca) channel inhibitor nifedipine or neurotransmitter L-glutamate, on the contraction of the tracheal smooth muscle provoked by acetylcholine (Ach) or potassium chloride (KCl) solution (85 mmol). METHOD: A section of rabbit trachea smooth muscle (diameter 2-3 mm) was put in a chamber with Krebs solution and continuous administration of gas with consistency 95% O2 and 5% CO2. One edge of the section was fixed while the other was connected to a transducer. The muscle contraction was recorded by a universal oscillograph (Harvard). RESULTS: Sodium nitroprusside induced relaxation of the Ach provoked contraction which was not dependent on the Ca ion in the extracellular space. The sodium nitroprusside induced relaxation was more pronounced when KCl was used to provoke contraction instead of Ach. Nifedipine in a concentration of 10 μM relaxed the Ach provoked contraction of the tracheal smooth muscles by 42% in all cases. L- glutamate in a concentration of 1 mM reduced by 47% the contraction provoked by KCl. The bronchodilator efficacy of the above three substances was significantly decreased (P <0.001) in the presence of methylene blue in a concentration of 10 μM. NO activates guanylate cyclase and this results in an increase of c-GMP which provokes relaxation of the smooth muscle. Methylene blue reverses this action of c-GMP previously activated by NO. CONCLUSIONS: NO is an important secondary transmittor of tracheal smooth muscle relaxation. It prevents the exit of Ca from the intracellular stores and inhibits the release of Ca from the membrane voltage-dependent receptors of smooth muscle cells. NO is a secondary messenger for some neurotransmittors such as glutamate, to act intracellularly.