Nitric oxide as a local mediator of prostaglandin F2α-induced regression in bovine corpus luteum:: An in vivo study

To test whether nitric oxide (NO) is involved in prostaglandin (PG) F-2alpha-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-2alpha (aPGF(2alpha); 5 mg/0.5 h); Group III, Nomega-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(2alpha). (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(2alpha) increased P-4 (P < 0.05), PGE(2) (P < 0.001), and LTC4 (P < 0.05) concentrations; L-NAME increased P-4 (P < 0.05) but did not change PGE(2) and LTC4 (P > 0.05) concentrations as compared with the period before treatment. Simultaneous perfusion of CL with L-NAME and aPGF(2alpha) caused a further increase of P-4 concentration (P < 0.05) induced by L-NAME or aPGF(2alpha) treatment and increased PGE(2) and LTC4 (P < 0.001) concentrations to the level observed after aPGF2. treatment. Perfusion of CL with aPGF(2alpha) 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(2)alpha treatment partially counteracted (P < 0.05) the luteal regression caused by aPGF(2alpha) 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(2alpha) may be mediated by NO as an important component of an autocrine/paracrine luteolytic cascade.