2‐methoxyestradiol mediates a greater coronary arterial relaxation response than 17beta‐estradiol in old female pigs

The protective effects of 17β‐estradiol against coronary artery disease may partially be due to the action of its metabolites. The objective of this study was to determine the arterial relaxation induced by the metabolites of 17β‐estradiol using coronary arteries obtained from old female Yorkshire retired breeding pigs (3–4 years old). These pigs demonstrated reproductive failures and/or a decline in litter size. The right coronary artery was dissected from each heart, and then sectioned into 3 mm rings which were suspended in organ baths. The rings were pre‐constricted with a 60mM K + solution before generating a concentration‐response relationship (10‐6 to 10‐4M) to 17β‐estradiol, 17α‐estradiol, 2‐hydroxyestradiol (2‐OHE), and 2‐methoxyestradiol (2‐MeOH). Arterial relaxation was initially demonstrated at 10‐5M for all the agonists; however, only the 2‐MeOH‐induced relaxation (27.47±5.90%) was greater than the other agonists at this concentration. The maximum relaxation achieved at 10‐4M was: 2‐MeOH (90.40±3.48%) > 17β‐estradiol (62.85±8.00) > 2‐OHE (49.30±11.12) > 17α‐estradiol (37.41±4.25). The selective estradiol receptor antagonists (10‐5M), tamoxifen and ICI 182,780, did not effect the relaxation response to 2‐MeOH. These data contrast results obtained using coronary arteries from market‐age pigs (6–9 months) in which the 17β‐estradiol‐induced relaxation occurred at much lower concentrations; thus suggesting that the arterial responsiveness to 17β‐estradiol decreases with age. In addition, our results suggest that the potent 2‐MeOH‐induced relaxation is not mediated by the “classical” estradiol‐mediated receptor mechanisms in old pigs. Support: UCA Research Council.