Exogenous estrogen rapidly attenuates pulmonary artery vasoreactivity and acute hypoxic pulmonary vasoconstriction

Tim Lahm, Paul R. Crisostomo, Troy A. Markel, Meijing Wang, Yue Wang, Brent Weil, Daniel R. Meldrum

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Chronic estrogen exposure has been shown to affect pulmonary artery (PA) vasoreactivity. However, the immediate effects of exogenously administered 17β-estradiol (E2) on vasopressor-induced PA vasoconstriction and acute hypoxic pulmonary vasoconstriction (HPV) have not yet been investigated. We hypothesized that exogenously administered E2 attenuates PA vasoreactivity and acute HPV through a rapid mechanism. Isometric force displacement was measured in isolated PA rings from proestrus female adult Sprague-Dawley rats, estrus, metestrus, or diestrus female adult Sprague-Dawley rats, and male adult Sprague-Dawley rats. The vasoconstrictor response in the absence of hypoxia (organ bath bubbled with 95% O2/5% CO2) was measured after stimulation with 1 μM of phenylephrine. Hypoxia was generated by changing the gas to 95% N2/5% CO2. The E2 was added to the organ bath in 0.1-nM, 0.5-nM, 1 -μM, 500-μM, and 1-mM doses. The 1-mM dose caused an immediate decrease in force in PA rings from estrus, metestrus, or diestrus female adult Sprague-Dawley rats. In addition, 500 μM and 1 mM of E2 attenuated phenylephrine- and hypoxia-induced vasoconstriction and potentiated the vasodilatory phase of hypoxia. These effects were immediate and independent of sex or estrous cycle. Lower E2 doses did not mediate any significant effects. We conclude that high doses of exogenous E2 acutely attenuate PA vasoreactivity and acute HPV in a rapid and dose-dependent manner. A better understanding of how E2 modulates the pulmonary vasomotor response may allow for future therapeutic interventions in acute pulmonary hypertensive crises or in pulmonary arterial hypertension.

Original languageEnglish (US)
Pages (from-to)660-667
Number of pages8
JournalShock
Volume30
Issue number6
DOIs
StatePublished - Dec 2008

Keywords

  • 17β-estradiol
  • Estrous cycle
  • Nongenomic effects
  • Phenylephrine
  • Sex differences
  • Sex hormones

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Emergency Medicine

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