Nitric Oxide as a Local Mediator of Prostaglandin F 2α -Induced Regression in Bovine Corpus Luteum: An In Vivo Study

Abstract

To test whether nitric oxide (NO) is involved in prostaglandin (PG) F_2α-induced regression of the bovine corpus luteum (CL) in vivo, heifers were treated as follows: Group 1, saline (3 ml/h); Group 2, dinoprost, an analogue of prostaglandin F_2α (aPGF_2α; 5 mg/0.5 h); Group III, Nω-nitro-L-arginine methyl ester (L-NAME; 200 mg/4 h), an inhibitor of nitric oxide synthase; and Group IV, L-NAME (400 mg/4 h) and aPGF_2α (5 mg/0.5 h). All treatments were administered by an intraluteal microdialysis system (MDS) on day 15 of the cycle. Perfusate and jugular plasma samples were collected at half-hour intervals; additionally, jugular plasma samples were collected once daily from day 16 to day 21 of the cycle. In the perfusate samples, aPGF_2α increased P₄ (P < 0.05), PGE₂ (P < 0.001), and LTC₄ (P < 0.05) concentrations; L-NAME increased P₄ (P < 0.05) but did not change PGE₂ and LTC₄ (P > 0.05) concentrations as compared with the period before treatment. Simultaneous perfusion of CL with L-NAME and aPGF_2α caused a further increase of P₄ concentration (P < 0.05) induced by L-NAME or aPGF_2α treatment and increased PGE₂ and LTC₄ (P < 0.001) concentrations to the level observed after aPGF_2α treatment. Perfusion of CL with aPGF_2α caused luteal regression within 24 h, while perfusion with L-NAME prolonged the life span of CL to day 21 (P < 0.05). Concomitant L-NAME and aPGF_2α treatment partially counteracted (P < 0.05) the luteal regression caused by aPGF_2α administration. These results show that NO is involved in the process of luteolysis in the bovine CL and suggest that the luteolytic effect of aPGF_2α may be mediated by NO as an important component of an autocrine/paracrine luteolytic cascade.