title: Estradiol potentiates the vasopressor response of the isolated perfused rat lung to the thromboxane mimic U-46619.
abstract: The high incidence of primary pulmonary hypertension in young women suggests a role of female sex hormones in the pathogenesis of this disease. Thromboxane A2 is a potent pulmonary vasoconstrictor, and a possible mediator of pulmonary hypertension. We studied the pulmonary vascular expression of thromboxane in isolated perfused lungs from sexually mature male and female rats, as well as the modulation of this expression by estrogen. Our data show that lungs from female rats exhibited a significantly (P less than .05) greater pressor response to the thromboxane mimic U46619, but not to angiotensin II, than those from their male cohorts. The difference in the response to U46619, however, was abolished by indomethacin (10 microM). Addition of 10 nM concentrations of estradiol 17-beta or diethylstilbestrol to the perfusate significantly potentiated (55 and 63%, respectively) the pressor response to U46619. Similarly, perfusion with diethylstilbestrol enhanced the pressor response to angiotensin II (70%). Estradiol 17-alpha or testosterone, however, were ineffective at similar concentrations. Ovariectomy, on the other hand, depressed, whereas chronic administration of estradiol 17-beta enhanced the pressor response to the thromboxane mimic, but had no effect on the response to angiotensin II. These data show a gender difference in pulmonary vascular expression of thromboxane in isolated perfused rat lungs, possibly modulated by estradiol. Thus, changes in estradiol levels may play a role in the development of primary pulmonary hypertension in young women.
authors.affiliation: Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC.
authors.forename: M Y
authors.initials: MY
authors.lastname: Farhat
authors.forename: P W
authors.initials: PW
authors.lastname: Ramwell
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000187:drug effects*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D004958:Estradiol; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D007213:Indomethacin