Nitric oxide differentially attenuates microvessel response to hypoxia and hypercapnia in injured lungs

Katsuhiko Naoki, Kazuhiro Yamaguchi, Koichi Suzuki, Hiroyasu Kudo, Kazumi Nishio, Nagato Sato, Kei Takeshita, Yukio Suzuki, Harukuni Tsumura

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9 Citations (Scopus)


The issue of whether the acinar microvessel response to alveolar hypoxia and hypercapnia is impaired in injured lungs has not been vigorously addressed, despite the importance of knowing whether it is or not when treating patients with serious lung injury in terms of permissive hypercapnia. Applying a real-time laser confocal luminescence microscope, we studied hypoxia- and hypercapnia-induced changes in the diameter of the intra-acinar arterioles, venules, and capillaries of isolated rat lungs harvested from animals exposed for 48 h to 21% O2 (group N) or 90% O2 (group H). Measurements were made with and without inhibition of nitric oxide (NO) synthase (NOS) by N(ω)-nitro-L-arginine methyl ester or of cyclooxygenase (COX) by indomethacin at different basal vascular tones evoked by thromboxane A2 (TXA2) analog. Hypoxia in the absence of TXA2 contracted arterioles in group N but not in group H. Attenuated hypoxia-induced arteriole constriction was restored almost fully by inhibiting NOS and partially by inhibiting COX. Hypercapnia induced venule dilation in group N, but did not dilate venules in group H, irrespective of TXA2. NOS inhibition in hypercapnia unexpectedly enhanced venule and arteriole dilation in group H. These responses no longer occurred when NOS and COX were inhibited simultaneously. In conclusion, microvessel reactions to hypoxia and hypercapnia are abnormal in hyperoxia-injured acini, in which NO directly attenuates hypoxia-induced arteriole constriction, whereas COX inhibited by excessive NO impedes hypercapnia-induced microvessel dilation.

Original languageEnglish
Pages (from-to)R181-R189
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number1 46-1
Publication statusPublished - 1999 Jul
Externally publishedYes


  • Acinar microcirculation
  • Confocal microscope
  • Cyclooxygenase
  • Hypercapnia
  • Hyperoxic lung injury
  • Hypoxia
  • Nitric oxide synthase

ASJC Scopus subject areas

  • Medicine(all)


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