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

Rat pulmonary arterial rings (phenylephrine pre-contracted), were relaxed b y carbachol or thapsigargin, or were contracted by N omega-nitro-L-arginine methyl ester (L-NAME). Mild hypoxia (41 mm Hg) attenuated the carbachol-in duced relaxation, whereas the relaxant and contractile effects produced by thapsigargin and r-NAME were unaffected. More severe hypoxia (20 mm Hg) abo lished thapsigargin-induced relaxation, with no further change in responses to carbachol or L-NAME. At 7 mm Hg, carbachol-induced relaxation was compl etely inhibited, and the L-NAME-induced contraction was attenuated but not abolished. The present data is consistent with the conclusion that nitric o xide (NO) synthase activity is less susceptible to oxy;:en deprivation unde r basal conditions than during activation. (C) 1999 Elsevier Science B.V. A ll rights reserved.