Radical-Mediated Pulmonary Lesions

Chronic hypoxia causes pulmonary arterial smooth muscle cell depolarisation, elevated endothelin-1, and vasoconstriction. Resting [Ca li in smooth muscle cells from intrapulmonary arteries of rats exposed to 10 % O2 for 21 days was 293.9 25.2 nM (vs. 153.6 28.7nM in normoxia) (Shimoda et al. 2000). Resting [Ca ] was decreased after extracellular Ca removed but not with nifedipine (10 M), an L-type Ca channel antagonist. After chronic hypoxia, the endothelin-1-induced increase in [Ca ]i was reduced and was aboHshed after extracellular Ca removal or nifedipine. Removal of extracellular Ca reduced endothehn-1-induced tension however, nifedipine had only a slight effect. 

There is substantial evidence that charmel activity and vascular tone can be modulated by reducing and oxidising agents. The importance of reduction-oxidation (redox) potential of key sulf-hydryl groups in the gating mechanism of certain 

Overactivation of glutamate receptors can contribute to a wide variety of lesions, including acute pulmonary oedema (Said et al. 1996), airway hyperesponsiveness (Said 1999) and inflammation. Blocking of the N-methyl-D-aspartate subtype of glutamate receptors by dizocilpine maleate (MK-801 10 pM) attenuated oxidant injury induced by paraquat (100 mg/kg to the pulmonary circulation) or by xanthine oxidase (Said et al. 2000). 

In primary cell cultures from the tunica media of human pulmonary arteries, hypoxia inhibited platelet-derived growth factor-induced [ Hjgluco-samine incorporation in secreted glycosaminogly-cans, especially hyaluronic acid, in vascular smooth muscle cells (Papakonstantinou et al. 2000). In contrast, it stimulated glycosaminoglycan secretion, specially heparan sulphate, by fibroblasts. 

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