Nitric oxide in asthma therapy.
The discovery of the delicate role of endogenous nitric oxide in the homeostasis of various cellular functions and the dynamic behaviour of the airways, has led to a new, rapidly progressing area of physiological science, that has direct bearing for our understanding of multiple airway diseases. The potentially protective effects of nitric oxide include: neuromodulation by mediating inhibitory non-cholinergic non-adrenergic nerve activity; smooth muscle relaxation, attenuating airway hyperresponsiveness to bronchoconstrictor stimuli and immune-suppression. NO itself or SNO can be administered directly to the airways, and the development of gene transfer therapy seems to become a realistic approach in the treatment of airway diseases. However, NO has also harmful effects, especially when it interacts with other molecules. At present, there are novel opportunities to modulate nitric oxide-synthesis aimed to restore the balance between the protective and deleterious effects of nitric oxide. This is potentially beneficial in both airway and alveolar diseases. Such interventions might be targeted in various ways, e.g. by using selective reactive nitrogen- and oxygen- scavengers, selective NO donors and selective nitric oxide synthase inhibitors. The possible therapeutical opportunities are reviewed in this paper. Nitric oxide has already made it from the bench to the bedside, and it is likely that new developments in this area will drastically change respiratory medicine during the coming 5-10 years.
Folkerts
Gert
G
Department of Pharmacology & Physiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands. G.Folkerts@pharm.uu.nl
Nijkamp
Frans P
FP
D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism*; D001993:Bronchodilator Agents / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism
D001993:Bronchodilator Agents; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase