Progesterone regulation of vascular thromboxane A(2) receptors in rhesus monkeys.
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.
Minshall
R D
RD
Division of Reproductive Sciences, Oregon Regional Primate Research Center, Beaverton 97006, USA.
Pavcnik
D
D
Halushka
P V
PV
Hermsmeyer
K
K
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
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