The effects of estrogen on pulmonary artery vasoreactivity and hypoxic pulmonary vasoconstriction: potential new clinical implications for an old hormone.
OBJECTIVE
Recent research recognizes gender as a major factor determining the outcomes in trauma, ischemia/reperfusion, shock, and sepsis. In particular, estrogen has been demonstrated to exert protective effects in these settings. The effects of estrogens on the pulmonary vasculature are potent and complex yet not fully understood. A better mechanistic understanding may allow for future therapeutic interventions in pulmonary hypertensive crises after cardiac surgery and during acute lung injury as well as in patients with pulmonary arterial hypertension.


METHODS
We searched PubMed for articles in the English language by using the search words pulmonary hypertension, hypoxic pulmonary vasoconstriction, estrogen, estradiol, inflammation, acute injury, ischemia reperfusion, sepsis, trauma, and burns. These were used in various combinations. We read the abstracts of the relevant titles to confirm their relevance, and the full articles were then extracted. References from extracted articles were checked for any additional relevant articles.


METHODS
Estrogen plays a critical role in the improved outcomes in the settings of trauma, shock, sepsis, myocardial ischemia/reperfusion, and acute lung injury. Several new mechanisms of action have been identified. In the pulmonary vasculature, estrogen causes vasodilation and attenuates the vasoconstrictor response to various stimuli, including hypoxia. This is mediated by increased levels of prostacyclin and nitric oxide as well as decreased levels of endothelin-1. In addition, effects on intracellular signaling pathways and several kinases as well as anti-inflammatory mechanisms may contribute as well. Recent studies suggest the importance of acute, nongenomic effects.


CONCLUSIONS
Estrogen exerts a variety of nongenomic actions, which may allow for future therapeutic interventions in pulmonary vascular disease.
Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
Tim
T
Lahm
Paul R
PR
Crisostomo
Troy A
TA
Markel
Meijing
M
Wang
Brent R
BR
Weil
Nathan M
NM
Novotny
Daniel R
DR
Meldrum
D000818:Animals; D004195:Disease Models, Animal; D004958:Estradiol / Q000378:metabolism / Q000502:physiology / Q000627:therapeutic use*; D004967:Estrogens / Q000096:biosynthesis / Q000378:metabolism / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D008297:Male; D012128:Respiratory Distress Syndrome / Q000188:drug therapy*; D014661:Vasoconstriction / Q000187:drug effects
D004967:Estrogens; D004958:Estradiol