Luteotrophic and luteolytic effects of nitric oxide in sheep are dose-dependent in vivo

It has been suggested that nitric oxide (NO) acts in either an anti-luteolytic or in a luteolytic manner, but the mechanism for these opposing roles is unclear. We hypothesized that NO may act in a dose-dependent manner to regulate luteal function, whereby low concentrations of NO might stimulate luteal progesterone production (i.e. luteotrophic) and high concentrations of NO might reduce concentrations of plasma progesterone (i.e. luteolytic). To test this hypothesis we infused increasing concentrations of the fast-acting NO donor, dipropylenetriamine NONOate (DPTA), into the arterial supply of sheep with ovarian transplants bearing a corpus luteum (CL). Infusions were performed on sheep with CL 11 days of age (n = 9) or over 30 days of age (n = 15). We measured changes in the concentration of progesterone in ovarian venous plasma during the 1-h infusion and for 24 h after the infusion, and then compared the mean concentration of progesterone between treatment groups for effects by dose and dose by period interactions. Compared with saline-treated controls (n = 6), the highest dose of 1000 μg/min DPTA (n = 6) reduced (P ≤ 0.05) the mean concentration of progesterone after the infusion. In sheep bearing a CL over 30 days of age, the 10 μg/min DPTA dose (n = 3) markedly increased (P ≤ 0.05) the mean concentration of progesterone both during and after the infusion, whereas the 100 μg/min DPTA dose (n = 3) increased (P ≤ 0.05) the mean concentration of progesterone only during the 1-h infusion. The mean concentration of progesterone was not different (P > 0.05) in sheep infused with the lowest dose of 1 μg/min DPTA (n = 6) compared with controls. We conclude that NO regulates luteal function in a dose-dependent manner in sheep in vivo.