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 post-menopausal [ovariec tomized (Ovx)] rhesus monkeys without progesterone replacement and after 2- wk progesterone treatment (1-2 ng/ml). In untreated Ovx animals, 100 mu mol /l serotonin + 1 mu mol/l U-46619 (syringe concentrations) provoked vasospa sm-like constrictions in six of six monkeys; zero of six progesterone-treat ed monkeys developed vasospasms. Sustained Ca2+ responses in vascular muscl e cells isolated from Ovx coronaries (208 +/- 63% of basal 20 min after sti mulation) treated with serotonin + U-46619 contrasted with transient Ca2+ r esponses (143 +/- 18% of basal and decreasing 5 min after stimulation) in p rogesterone-treated monkeys. The maximum density of [1S-(1I,2J-(5Z),3I(1E,3 R*),4I)]-7-[3-(3-hydroxy-4-(4'- [I-125]iodophenoxy)-1-butenyl)-7-oxabicyclo [2.2.1]heptan-2-yl]-5-heptenoic. acid ([I-125] -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 c an decrease arterial TxA(2)R in Ovx monkeys.