Chronic hypoxia causes oxidative injury of pulmonary vessels and attenuates their reactivity to different stimuli. When combined with hypercapnia, biochemical markers of this injury are reduced but the effect of concomitant hypoxia and hypercapnia on vascular reactivity is not fully understood. This study was therefore designed to test whether hypercapnia can prevent also the hypoxia-induced loss of reactivity of pulmonary vessels. The reactivity of vessels from rats exposed either to hypoxia or hypoxia combined with hypercapnia was tested using a small vessel myograph (M 500A, Linton, Norfolk, GB). The second and third intrapulmonary branches of pulmonary arteries were isolated under a dissecting microscope from lungs of 8 control rats (group N), 6 rats exposed to hypoxia for 5 days (isobaric, 10 % O(2), group H) and 7 rats exposed to hypoxia combined with hypercapnia for 5 days (10 % O(2), 5 % CO(2), group H+CO(2)). The transmural pressure was set by automatic normalization to 30 mm Hg. The vessel size did not vary among the groups. After stabilization we challenged the vessels twice with KCl (80 mM) and once with PGF(2alpha) (0.1 mM). There were no significant differences in KCl induced contractions among the groups. The responses to PGF(2alpha) were expressed as a ratio to the maximal tension obtained by the exposure to 80 mM KCl. Contractions induced by PGF(2alpha) were markedly reduced in group H (0.07+/-0.02) and in group H+CO(2) (0.26+/-0.03) in comparison with group N (0.83+/-0.07). The vessels of group H responded to PGF(2alpha) less than those of group H+CO(2). However we observed the attenuated reactivity also in group H+CO(2) in comparison with N. Hypercapnia therefore partially blunted the hypoxia-induced loss of reactivity in pulmonary arteries. This finding supports the hypothesis that hypercapnia significantly alters the nature of lung injury induced by chronic hypoxia.

Department of Pathophysiology 2nd Faculty of Medicine Charles University Prague Czech Republic

Department of Physiology 2nd Faculty of Medicine Charles University Prague Czech Republic

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