title: Administration of a nitric oxide synthase inhibitor counteracts prostaglandin F2-induced luteolysis in cattle.
abstract: 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 F2alpha (PGF2alpha)-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 PGF2alpha-induced regression of the CL, saline (10 ml/h; n = 10) or a nonselective NOS inhibitor (Nomega-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 PGF2alpha (aPGF2alpha; 100 microg) 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 aPGF2alpha 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 aPGF2alpha were higher (P < 0.05) than in animals injected only with aPGF2alpha. The PGF2alpha 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 aPGF2alpha (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 PGF2alpha.
authors.affiliation: Division of Reproductive Endocrinology and Pathophysiology, Institute of Animal Reproduction and Food Research, PAS, Olsztyn 10-747, Poland. skadar@pan.olsztyn.pl
authors.forename: Dariusz J
authors.initials: DJ
authors.lastname: Skarzynski
authors.forename: Jerzy J
authors.initials: JJ
authors.lastname: Jaroszewski
authors.forename: Mamadou M
authors.initials: MM
authors.lastname: Bah
authors.forename: Katarzyna M
authors.initials: KM
authors.lastname: Deptula
authors.forename: Beata
authors.initials: B
authors.lastname: Barszczewska
authors.forename: Barbara
authors.initials: B
authors.lastname: Gawronska
authors.forename: William
authors.initials: W
authors.lastname: Hansel
mesh_terms: D000818:Animals; D002417:Cattle; D015237:Dinoprost / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D030762:Estrous Cycle / Q000502:physiology; D005260:Female; D007150:Immunohistochemistry; D003341:Luteolysis / Q000187:drug effects*; D009252:NADPH Dehydrogenase / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D009573:Nitrites / Q000097:blood; D011374:Progesterone / Q000097:blood
chemical_list: D004791:Enzyme Inhibitors; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D011374:Progesterone; D015237:Dinoprost; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D009252:NADPH Dehydrogenase; D019331:NG-Nitroarginine Methyl Ester