title: Intrauterine infusion of BQ-610, an endothelin type A receptor antagonist, delays luteolysis in dairy heifers.
abstract: Three separate in vivo experiments were conducted to evaluate the putative role of endothelin-1 (ET-1) during luteal regression in heifers. In Experiment 1, a single intraluteal injection of 500 microg BQ-610 [(N,N-hexamethylene) carbamoyl-Leu-D-Trp (CHO)-D-Trp], a highly specific endothelin A (ETA) receptor antagonist, did not diminish the decline in plasma progesterone following a single exogenous injection of 25 mg prostaglandin F2 alpha (PGF2alpha) administered at midcycle of the estrous cycle. In Experiment 2, six intrauterine infusions of 500 microg BQ-610 given every 12 h on days 16-18 delayed spontaneous luteolysis, as evidenced by an extended elevation (P=0.054) of plasma progesterone concentration. In Experiment 3, heifers were administered six intrauterine infusions of BQ-610 or saline on days 16-19, and peripheral blood samples were collected from day 11 to 16 (before infusion), hourly on days 16-19 (during infusion), and on days 20-25 (after infusion). BQ-610 treated heifers had markedly higher (P<0.0001) levels of plasma progesterone compared with saline controls, and this effect was most notable during the infusion period (treatment by period interaction; P<or=0.05). Heifers infused with BQ-610 also had higher progesterone levels on day 21 (treatment by time interaction; P<or=0.05). Mean plasma concentrations of 13,14-dihydro-15-keto-PGF2alpha (PGFM), the primary metabolite of PGF2alpha, were measured in the samples collected hourly and were not different (P>or=0.05) between treatments. These results indicate that the in vivo antagonism of the ETA receptor can delay functional luteolysis, and supports the theory that ET-1 regulates luteal function in ruminants.
authors.affiliation: Department of Animal Science, University of Connecticut, 3636 Horsebarn Hill Road Extension, Storrs, CT 06269-4040, United States. keatorc@ohsu.edu
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Keator
authors.forename: David T
authors.initials: DT
authors.lastname: Schreiber
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Hoagland
authors.forename: John A
authors.initials: JA
authors.lastname: McCracken
authors.forename: Robert A
authors.initials: RA
authors.lastname: Milvae
mesh_terms: D000282:Administration, Intravaginal; D000818:Animals; D002417:Cattle / Q000502:physiology*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D004305:Dose-Response Relationship, Drug; D065130:Endothelin A Receptor Antagonists; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D003341:Luteolysis / Q000097:blood / Q000187:drug effects*; D009842:Oligopeptides / Q000008:administration & dosage*; D011374:Progesterone / Q000097:blood; D013997:Time Factors; D014599:Uterus / Q000187:drug effects*
chemical_list: D065130:Endothelin A Receptor Antagonists; D009842:Oligopeptides; C087220:BQ 610; C008228:15-keto-13,14-dihydroprostaglandin F2alpha; D011374:Progesterone; D015237:Dinoprost