title: Progesterone regulation of vascular thromboxane A(2) receptors in rhesus monkeys.
abstract: We hypothesized that progesterone regulates thromboxane A(2) receptor (TxA(2)R) density in primate vascular muscle and that TxA(2)R density correlates with coronary reactivity in vivo and in vitro. Reactivity to serotonin + U-46619 was determined by angiography in surgically postmenopausal [ovariectomized (Ovx)] rhesus monkeys without progesterone replacement and after 2-wk progesterone treatment (1-2 ng/ml). In untreated Ovx animals, 100 micromol/l serotonin + 1 micromol/l U-46619 (syringe concentrations) provoked vasospasm-like constrictions in six of six monkeys; zero of six progesterone-treated monkeys developed vasospasms. Sustained Ca(2+) responses in vascular muscle cells isolated from Ovx coronaries (208 +/- 63% of basal 20 min after stimulation) treated with serotonin + U-46619 contrasted with transient Ca(2+) responses (143 +/- 18% of basal and decreasing 5 min after stimulation) in progesterone-treated monkeys. The maximum density of [1S-(1I,2J(5Z),3I(1E,3R*),4I)]-7-[3-(3-hydroxy-4-(4'-[(125)I]iodophenoxy)- 1-butenyl)-7-oxabicyclo[2.2.1]heptan-2-yl]-5-heptenoic acid ([(125)I]-BOP) binding was greater (P < 0.01) in carotid arteries and aortic membranes from Ovx (109 +/- 11 fmol/mg) compared with progesterone-treated (43 +/- 15 fmol/mg) monkeys. TxA(2)R immunolabeling revealed greater coronary TxA(2)R labeling in Ovx compared with progesterone-treated monkeys. The results suggest that progesterone can decrease arterial TxA(2)R in Ovx monkeys.
authors.affiliation: Division of Reproductive Sciences, Oregon Regional Primate Research Center, Beaverton 97006, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Minshall
authors.forename: D
authors.initials: D
authors.lastname: Pavcnik
authors.forename: P V
authors.initials: PV
authors.lastname: Halushka
authors.forename: K
authors.initials: K
authors.lastname: Hermsmeyer
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D003329:Coronary Vasospasm / Q000139:chemically induced; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D005260:Female; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D008253:Macaca mulatta; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D010052:Ovariectomy; D017698:Postmenopause / Q000502:physiology; D011374:Progesterone / Q000494:pharmacology / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology; D011869:Radioligand Assay; D017482:Receptors, Thromboxane / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D014661:Vasoconstriction / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000502:physiology
chemical_list: D017482:Receptors, Thromboxane; D014662:Vasoconstrictor Agents; D012701:Serotonin; D011374:Progesterone; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D011493:Protein Kinase C