Role of the L-arginine nitric oxide pathway in hypoxic fetoplacental vasoconstriction.

The role of nitric oxide in hypoxic fetoplacental vasoconstriction (HFPV) was investigated using dually perfused human placental cotyledons. Standard medium (Earle's salt solution with added dextran and L-arginine) was equilibrated with 95 per cent O2 and 5 per cent CO2 (maternal side) and 94 per cent N2 and 6 per cent CO2 (fetal side). Part 1 consisted of perfusion for 1 h, then maternal perfusate equilibrated with a 95 per cent N2 and 5 per cent CO2 for 20 min (hypoxia), and then the original perfusion conditions resumed for 40 min. In part 2, this sequence was repeated with standard medium alone (n = 6), or with added N-nitro-L-arginine methyl ester (L-NAME) (n = 6), or L-NAME and nitroglycerin (n = 6). When standard medium was used throughout, basal fetal perfusion pressure (30 +/- 2 mmHg) and the hypoxia-induced increase in perfusion pressure (18 +/- 1 mmHg) did not change significantly between parts 1 and 2. L-NAME increased basal perfusion pressure from 33 +/- 3 to 56 +/- 2 mmHg whereas perfusion pressure remained unchanged with L-NAME and nitroglycerin or nitroglycerin alone. The hypoxic vasoconstriction observed during part 1 in the L-NAME (14 +/- 3 mmHg) and the L-NAME with nitroglycerin groups (18 +/- 2 mmHg) was abolished during part 2 (to - 4 +/- 1 and 0.4 +/- 0.5 mmHg, respectively) whereas nitroglycerin alone significantly blunted the response (21 +/- 3 to 6 +/- 1 mmHg). Results suggest that a reduction in basal NO release mediates hypoxic fetoplacental vasoconstriction in the perfused human placental cotyledon in vitro.