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This Article Full Text Full Text (PDF) All Versions of this Article: 68/5/1674    most recent biolreprod.102.008573v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Skarzynski, D. J. Articles by Hansel, W. Search for Related Content PubMed PubMed Citation Articles by Skarzynski, D. J. Articles by Hansel, W. Agricola Articles by Skarzynski, D. J. Articles by Hansel, W.

Administration of a Nitric Oxide Synthase Inhibitor Counteracts Prostaglandin F₂-Induced Luteolysis in Cattle¹

Division of Reproductive Endocrinology and Pathophysiology,³ Institute of Animal Reproduction and Food Research, PAS, Olsztyn 10-747, Poland Department of Pharmacology,⁴ Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, Poland Pennington Biomedical Research Center,⁵ Louisiana State University, Baton Rouge, Louisiana 70808

The objective of this study was to determine whether nitric oxide (NO) is produced locally in the bovine corpus luteum (CL) and whether NO mediates prostaglandin F₂ (PGF₂)-induced regression of the bovine CL in vivo. The local production of NO was determined in early I, early II, mid, late, and regressed stages of CL by determining NADPH-d activity and the presence of inducible and endothelial NO synthase immunolabeling. To determine whether inhibition of NO production counteracts the PGF₂-induced regression of the CL, saline (10 ml/h; n = 10) or a nonselective NOS inhibitor (N-nitro-L-arginine methyl ester dihydrochloride [L-NAME]; 400 mg/h; n = 9) was infused for 2 h on Day 15 of the estrous cycle into the aorta abdominalis of Holstein/Polish Black and White heifers. After 30 min of infusion, saline or cloprostenol, an analogue of PGF₂ (aPGF₂; 100 µg) was injected into the aorta abdominalis of animals infused with saline or L-NAME. NADPH-diaphorase activity was present in bovine CL, with the highest activity at mid and late luteal stages (P < 0.05). Inducible and endothelial NO synthases were observed with the strongest immunolabeling in the late CL (P < 0.05). Injection of aPGF₂ increased nitrite/nitrate concentrations (P < 0.01) and inhibited P₄ secretion (P < 0.05) in heifers that were infused with saline. Infusion of L-NAME stimulated P₄ secretion (P < 0.05) and concomitantly inhibited plasma concentrations of nitrite/nitrate (P < 0.05). Concentrations of P₄ in heifers infused with L-NAME and injected with aPGF₂ were higher (P < 0.05) than in animals injected only with aPGF₂. The PGF₂ analogue shortened the cycle length compared with that of saline (17.5 ± 0.22 days vs. 21.5 ± 0.65 days P < 0.05). L-NAME blocked the luteolytic action of the aPGF₂ (22.6 ± 1.07 days vs. 17.5 ± 0.22 days, P < 0.05). These results suggest that NO is produced in the bovine CL. NO inhibits luteal steroidogenesis and it may be one of the components of an autocrine/paracrine luteolytic cascade induced by PGF₂.

¹ This research was supported by grants KBN 5P06K012 19 and KBN 5P06K 003 21 from the State Committee for Scientific Research and by The Gordon and Mary Cain Foundation.

² Correspondence: Dariusz J. Skarzynski, Division of Reproductive Endocrinology and Pathophysiology, Institute of Animal Reproduction and Food Research, PAS, Tuwima-St 10, Olsztyn 10-747, Poland. FAX: 48 89 524 03 47; skadar{at}pan.olsztyn.pl

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