Hypercapnia Attenuates the Hypoxia-Induced Blunting of the Reactivity in Chronically Hypoxic Rats

Abstract

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 % O2, group H) and 7 rats exposed to hypoxia combined with hypercapnia for 5 days (10 % O2, 5 % CO2, group H+CO2). 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 PGF2α (0.1 mM). There were no significant differences in KCl induced contractions among the groups. The responses to PGF2α were expressed as a ratio to the maximal tension obtained by the exposure to 80 mM KCl. Contractions induced by PGF2α were markedly reduced in group H (0.07±0.02) and in group H+CO2 (0.26±0.03) in comparison with group N (0.83±0.07). The vessels of group H responded to PGF2α less than those of group H+CO2. However we observed the attenuated reactivity also in group H+CO2 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.

Decreased collagen VI in the tunica media of pulmonary vessels during exposure to hypoxia: a novel step in pulmonary arterial remodeling

“…Moreover, we know from previous experiments that the type of isolated vessels, on which we centered our interest, is reactive to hypoxia and thus they are really involved in the process of the development of HPH. 27 Collagen VI concentration was reduced by four days of hypoxia exclusively around the cells in the tunica media of conduit pulmonary arteries. This specific local loss of collagen VI was confirmed by two independent methods: immunohistochemistry and 2-DE ( Figs.…”

“…Thus, we believe that the results from all the methods we used are comparable to each other. Moreover, we know from previous experiments that the type of isolated vessels, on which we centered our interest, is reactive to hypoxia and thus they are really involved in the process of the development of HPH 27 …”