Nitric oxide differentially attenuates microvessel response to hypoxia andhypercapnia in injured lungs

The issue of whether the acinar microvessel response to alveolar hypoxia an d hypercapnia is impaired in injured lungs has not been vigorously addresse d, despite the importance of knowing whether it is or not when treating pat ients with serious lung injury in terms of permissive hypercapnia. Applying a real-time laser confocal luminescence microscope, we studied hypoxia- an d hypercapnia-induced changes in the diameter of the intra-acinar arteriole s, venules, and capillaries of isolated rat lungs harvested from animals ex posed for 48 h to 21% O-2 (group N) or 90% O-2 (group H). Measurements were made with and without inhibition of nitric oxide (NO) synthase (NOS) by N- omega-nitro-L-arginine methyl ester or of cyclooxygenase (COX) by indometha cin at different basal vascular tones evoked by thromboxane A(2) (TXA(2)) a nalog. Hypoxia in the absence of TXA(2) contracted arterioles in group N bu t not in group H. Attenuated hypoxia-induced arteriole constriction was res tored almost fully by inhibiting NOS and partially by inhibiting COX. Hyper capnia induced venule dilation in group N, but did not dilate venules in gr oup H, irrespective of TXA(2). NOS inhibition in hypercapnia unexpectedly e nhanced venule and arteriole dilation in group H. These responses no longer occurred when NOS and COX were inhibited simultaneously. In conclusion, mi crovessel reactions to hypoxia and hypercapnia are abnormal in hyperoxia-in jured acini, in which NO directly attenuates hypoxia-induced arteriole cons triction, whereas COX inhibited by excessive NO impedes hypercapnia-induced microvessel dilation.