Fig. 2.

Chronic hypoxia ablates the ability of Protein Kinase G to inhibit serotonergic contractile tone (expressed relative to the maximum contractile tone produced in response to 120 mM K⁺) in ovine fetal middle cerebral arteries. Concentration-response determinations for serotonin were determined in vitro in the presence and absence of a cell permeant and non-metabolizable activator of Protein Kinase G, and then converted to occupancy-response curves using parallel measurements of agonist binding affinity. PKG activation potently inhibited serotonergic tone independent of changes in serotonergic receptor density or affinity in arteries from normoxic, but not chronically hypoxic, term fetuses. Chronic hypoxia was imposed on the fetuses by maintaining pregnant ewes at 3820m for the final 110 days of gestation. Error bars indicate SEM for N≥6.