Progesterone regulation of vascular thromboxane A₂ receptors in rhesus monkeys

We hypothesized that progesterone regulates thromboxane A₂ receptor (TxA₂R) density in primate vascular muscle and that TxA₂R density correlates with coronary reactivity in vivo and in vitro. Reactivity to serotonin + U-46619 was determined by angiography in surgically post-menopausal [ovariectomized (Ovx)] rhesus monkeys without progesterone replacement and after 2-wk progesterone treatment (1-2 ng/ml). In untreated Ovx animals, 100 μmol/l serotonin + 1 μmol/l U-46619 (syringe concentrations) provoked vasospasm-like constrictions in six of six monkeys; zero of six progesterone-treated monkeys developed vasospasms. Sustained Ca²⁺ 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 Ca²⁺ responses (143±18% of basal and decreasing 5 rain after stimulation) in progesterone-treated monkeys. The maximum density of [1S-(1/,2J-(5Z),3/(1E, 3R*),4I)]-7-[3-(3-hydroxy- 4-(4′-[¹²⁵I]iodophenoxy)-1-butenyl)-7-oxabicyclo [2.2.1]heptan-2-yl]-5-heptenoic acid ([¹²⁵I]-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. TxA₂R immunolabeling revealed greater coronary TxA₂R labeling in Ovx compared with progesterone-treated monkeys. The results suggest that progesterone can decrease arterial TxA₂R in Ovx monkeys.