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Am J Physiol Heart Circ Physiol 281: H1498-H1507, 2001;
0363-6135/01 $5.00
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Vol. 281, Issue 4, H1498-H1507, October 2001

Progesterone regulation of vascular thromboxane A2 receptors in rhesus monkeys

Richard D. Minshall1, Dusan Pavcnik2, Perry V. Halushka4, and Kent Hermsmeyer1,3

1 Division of Reproductive Sciences, Oregon Regional Primate Research Center, Beaverton 97006; 2 Dotter Interventional Institute and 3 Departments of Medicine and Cell and Developmental Biology, Oregon Health Sciences University, Portland, Oregon 97201; and 4 Division of Clinical Pharmacology, Department of Medicine, and Departments of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, South Carolina 29425

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 postmenopausal [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 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'-[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.

postmenopausal; vascular reactivity; coronary; ischemic heart disease


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