title: Exogenous estrogen rapidly attenuates pulmonary artery vasoreactivity and acute hypoxic pulmonary vasoconstriction.
abstract: Chronic estrogen exposure has been shown to affect pulmonary artery (PA) vasoreactivity. However, the immediate effects of exogenously administered 17beta-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 microM 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-microM, 500-microM, 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 microM 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.
authors.affiliation: Division of Pulmonary, Allergy, Critical Care and Occupational Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Tim
authors.initials: T
authors.lastname: Lahm
authors.forename: Paul R
authors.initials: PR
authors.lastname: Crisostomo
authors.forename: Troy A
authors.initials: TA
authors.lastname: Markel
authors.forename: Meijing
authors.initials: M
authors.lastname: Wang
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.forename: Brent
authors.initials: B
authors.lastname: Weil
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Meldrum
mesh_terms: D000818:Animals; D002245:Carbon Dioxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D000860:Hypoxia / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D004967:Estrogens; D014662:Vasoconstrictor Agents; D002245:Carbon Dioxide; D010656:Phenylephrine