title: Antiestrogens reduce plasma levels of endothelin-1 without affecting nitrate levels in breast cancer patients.
abstract: Tamoxifen protects against myocardial infarction through mechanisms that are poorly understood. We studied the effects of tamoxifen and another antiestrogen, toremifene, on the production of vasoconstrictive endothelin-1 and of vasodilatory nitric oxide in 44 postmenopausal patients with breast cancer. These started treatment, in randomized order, with either tamoxifen (20 mg/day; n = 25) or toremifene (40 mg/day; n = 19). Plasma samples collected before treatment and after 6 and 12 months of both regimens were assayed for endothelin-1 with a specific radioimmunoassay and for nitrite/nitrate with a method based on the Griess reaction. The antiestrogen group as a whole showed a fall in endothelin-1 at 6 months (5.9 +/- 3.3%; p = 0.06) (mean +/- SE) and at 12 months (7.1 +/- 5.5%; p = 0.03). This fall was solely due to toremifene, the use of which was associated with falls in endothelin-1 at 6 months (12.9 +/- 4.7%; p = 0.01) and 12 months (9.2 +/- 6.2%; p = 0.06). The antiestrogen regimen failed to affect plasma nitric oxide significantly but nevertheless the ratio between nitric oxide and endothelin-1 rose by 31.6 +/- 13.3% at 6 months and by 35.6 +/- 15.3% at 12 months in the antiestrogen users, an effect similar in the tamoxifen and toremifene groups. We conclude that antiestrogens may protect against myocardial infarction by preventing the release of endothelin-1 and by shifting the balance between nitric oxide and endothelin-1 to the dominance of the former. Our data predict that toremifene and tamoxifen at the doses studied here will provide similar cardiovascular protection.
authors.affiliation: Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Finland.
authors.forename: M B
authors.initials: MB
authors.lastname: Marttunen
authors.forename: P
authors.initials: P
authors.lastname: Hietanen
authors.forename: A
authors.initials: A
authors.lastname: Tiitinen
authors.forename: L
authors.initials: L
authors.lastname: Viinikka
authors.forename: O
authors.initials: O
authors.lastname: Ylikorkala
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy; D019332:Endothelin-1 / Q000097:blood*; D004965:Estrogen Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control; D009566:Nitrates / Q000097:blood*; D017698:Postmenopause; D013629:Tamoxifen / Q000494:pharmacology / Q000627:therapeutic use; D017312:Toremifene / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D019332:Endothelin-1; D004965:Estrogen Antagonists; D009566:Nitrates; D013629:Tamoxifen; D017312:Toremifene