Progesterone regulation of vascular thromboxane A2 receptors in rhesus monkeys

R. D. Minshall, D. Pavcnik, P. V. Halushka, K. Hermsmeyer

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)H1498-H1507
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume281
Issue number4 50-4
DOIs
StatePublished - Jan 1 2001

Keywords

  • Coronary
  • Ischemic heart disease
  • Postmenopausal
  • Vascular reactivity

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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