Intraluteal administration of a nitric oxide synthase blocker stimulates progesterone and oxytocin secretion and prolongs the life span of the bovine corpus luteum

To test the role of nitric oxide (NO) in secretory functions of bovine corpora lutea (CL), two groups of four Holstein heifers each were treated as follows: Group 1, N omega-Nitro-L-Arginine Methyl Ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), on Day 11 or 12 of the cycle and Group 2, L-NAME on Days 17 and 18 of the cycle. All treatments were administered by an intraluteal microdialysis system (MDS), Drugs were infused for 4-hr periods on the designated days, and the treatment periods were preceded and followed by 4-hr control periods. Perfusate and jugular blood samples were collected at half-hour intervals. Perfusate samples were analyzed for progesterone (P4), oxytocin (OT), prostaglandin F-2 alpha (PGF(2 alpha)), and leukotriene C-4 (LTC4); jugular plasma samples were analyzed for P-4, OT, and LH. Perfusion of L-NAME on Day 11 or 12 consistently increased P-4 concentration in the perfusate, but had no effect on the life span of the CL. Perfusion of L-NAME on Days 17-18 also elevated P-4 levels in the perfusate, and in addition, maintained P-4 levels in the plasma of three of the four treated animals through Day 25 of the cycle. L-NAME perfusion also increased OT release concomitant with P-4 into the perfusate at both the mid- and late-luteal phase treatments. For the most part, concentrations of LH, OT, and P-4 in the jugular plasma samples collected during the perfusions were unaffected by treatments. L-NAME perfusion caused small, but significant (P < 0.05) increases in perfusate PGF(2 alpha) and LTC4 at Days 17 and 18 and in LTC4 on Day 11 or 12. These data indicate that NO plays a direct luteolytic role in regression of the bovine CL.