Evidence for the differential sensitivity to hypoxia of basal and agonist-induced nitric oxide release

Rat pulmonary arterial rings (phenylephrine pre-contracted), were relaxed by carbachol or thapsigargin, or were contracted by Nomega-nitro-L-arginine methyl ester (L-NAME). Mild hypoxia (41 mm Hg) attenuated the carbachol-induced relaxation, whereas the relaxant and contractile effects produced by thapsigargin and L-NAME were unaffected. More severe hypoxia (20 mm Hg) abolished thapsigargin-induced relaxation, with no further change in responses to carbachol or L-NAME. At 7 mm Hg, carbachol-induced relaxation was completely inhibited, and the L-NAME-induced contraction was attenuated but not abolished. The present data is consistent with the conclusion that nitric oxide (NO) synthase activity is less susceptible to oxygen deprivation under basal conditions than during activation.