Inhalation of nitric oxide modulates methacholine-induced bronchoconstriction in the rabbit

Nitric oxide (NO) accounts for the major effects of endothelium-derived relaxing factor. We investigated whether NO, added to the inspired gas, could exert a bronchodilatory action similar to the pulmonary vasodilation described when administering NO during lung vascular constriction. New Zealand White rabbits were intubated and mechanically-ventilated with 30% oxygen during neuroleptanaesthesia. Methacholine (MCh) was nebulized at increasing concentrations from 0.5 to 4.0 mg.ml-1, with or without inhalation of 80 parts per million (ppm) NO. The technique of rapid airway occlusion during constant-flow inflation was used for measuring respiratory mechanics, i.e. resistance and compliance of the respiratory system. Methacholine nebulization without NO inhalation raised the resistance from 51 +/- 6 (mean +/- 95% confidence interval) to 107 +/- 52 cmH2O.l-1.s at Mch 4 mg.ml-1. During NO inhalation, nebulization of MCh showed no significant increase in resistance. Arterial oxygen tension (PaO2) and compliance fell to the same extent during methacholine challenge, whether NO was inhaled or not. Closure of small airways may be a mechanism that causes the decrease in PaO2 and compliance observed. This suggests that 80 ppm NO added to the inspired gas modulates the response in central airway tone to nebulized MCh in this rabbit model. However, it appears to have less effect on peripheral airways.

This article has been cited by other articles:

				M. Yang, D. Rangasamy, K. I. Matthaei, A. J. Frew, N. Zimmmermann, S. Mahalingam, D. C. Webb, D. J. Tremethick, P. J. Thompson, S. P. Hogan, et al. Inhibition of Arginase I Activity by RNA Interference Attenuates IL-13-Induced Airways Hyperresponsiveness J. Immunol., October 15, 2006; 177(8): 5595 - 5603. [Abstract] [Full Text] [PDF]

				F. L. M. Ricciardolo, P. J. Sterk, B. Gaston, and G. Folkerts Nitric Oxide in Health and Disease of the Respiratory System Physiol Rev, July 1, 2004; 84(3): 731 - 765. [Abstract] [Full Text] [PDF]

				A. M. Hamad, A. Clayton, B. Islam, and A. J. Knox Guanylyl cyclases, nitric oxide, natriuretic peptides, and airway smooth muscle function Am J Physiol Lung Cell Mol Physiol, November 1, 2003; 285(5): L973 - L983. [Abstract] [Full Text] [PDF]

				F L M Ricciardolo Multiple roles of nitric oxide in the airways Thorax, February 1, 2003; 58(2): 175 - 182. [Abstract] [Full Text] [PDF]

				G. Ramesh, S.K. Jindal, N.K. Ganguly, and V. Dhawan Increased nitric oxide production by neutrophils in bronchial asthma Eur. Respir. J., May 1, 2001; 17(5): 868 - 871. [Abstract] [Full Text] [PDF]

				Y.-L. Dong, L. Fang, P.R.R. Gangula, and C. Yallampalli Regulation of Inducible Nitric Oxide Synthase Messenger Ribonucleic Acid Expression in Pregnant Rat Uterus Biol Reprod, October 1, 1998; 59(4): 933 - 940. [Abstract] [Full Text]

				N. M. Tsoukias, Z. Tannous, A. F. Wilson, and S. C. George Single-exhalation profiles of NO and CO2 in humans: effect of dynamically changing flow rate J Appl Physiol, August 1, 1998; 85(2): 642 - 652. [Abstract] [Full Text] [PDF]

				P. M. Renzi, N. Sebastiao, A. S. Assaad, A. Giaid, and Q. Hamid Inducible Nitric Oxide Synthase mRNA and Immunoreactivity in the Lungs of Rats Eight Hours after Antigen Challenge Am. J. Respir. Cell Mol. Biol., July 1, 1997; 17(1): 36 - 40. [Abstract] [Full Text]