Ovarian steroid protection against coronary artery hyperreactivity in rhesus monkeys

Richard D. Minshall, Frank Z. Stanczyk, Koichi Miyagawa, Barry Uchida, Michael Axthelm, Miles Novy, Kent Hermsmeyer

Research output: Contribution to journalArticlepeer-review

77 Scopus citations


Our hypothesis was that estrogen and progesterone modulate coronary artery reactivity in rhesus monkeys. Adult ovariectomized (ovx) monkeys were treated for 1, 2, or 4 wk with physiological concentrations of 17β-estradiol (E2), natural progesterone (P), and/or therapeutic levels of medroxyprogesterone acetate (MPA). Steroid concentrations in venous blood, coronary artery estrogen receptor (ER) and progesterone receptor (PRI localization, and isolated vascular muscle cell (VMC) Ca2+ and protein kinase C responses to serotonin and U46619 (a thromboxane A2 mimetic) were measured. Ovx monkey VMC responses were hyperreactive, showing prolonged increases in intracellular Ca2+ and protein kinase C that correlated with exaggerated in vivo coronary artery vasoconstrictor responses. The hyperreactive Ca2+ responses were abolished by in vivo treatment with E2 and/or P. However, VMC from ovx monkeys treated with the combination of E2 and MPA or E2, P, and MPA remained hyperreactive to vasoconstrictor stimuli, suggesting that MPA negated the protective effects of E2. ER were detected primarily in interstitial and endothelial cells and a minor fraction of the VMC. PR were localized to coronary artery VMC and interstitial cell nuclei. In vivo treatment of ovx monkeys with E2 tended to up-regulate PR in VMC, but MPA appeared to down-regulate PR expression. These results suggest that E2 and P replacement decreases coronary artery reactivity through direct interactions with ER and PR in coronary artery VMC.

Original languageEnglish (US)
Pages (from-to)649-659
Number of pages11
JournalJournal of Clinical Endocrinology and Metabolism
Issue number2
StatePublished - 1998

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


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