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The estrogen metabolite, 2‐methoxyestradiol, attenuates coronary arterial tone by inhibiting the influx of calcium
Author(s) -
Babbs Keith,
Hill Brent J.F.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1381-d
Subject(s) - 2 methoxyestradiol , calcium , contraction (grammar) , estrogen , incubation , endocrinology , coronary arteries , medicine , metabolite , chemistry , voltage dependent calcium channel , agonist , artery , biochemistry , receptor
Estrogen can be rapidly metabolized to 2‐methyoxyestradiol (2ME) at the arterial wall. Like estrogen, 2ME has a relaxant effect on arteries; however, the exact mechanism is not known. We hypothesized that 2ME attenuates arterial tone by inhibiting calcium influx. Right coronary arteries were obtained from female pigs and sectioned into 3 mm denuded rings which were suspended in organ baths. A concentration‐response relationship to KCl (15 mM‐80 mM) was generated after a 60 min incubation in the presence and absence of various 2ME concentrations (10 −7 M to 10 −4 M). 2ME (10 −4 M) significantly inhibited the KCl depolarizing concentration‐response relationship. To determine the direct effect of 2ME on L‐type calcium channels, a similar experiment was conducted using 10 −5 M BayK8644, an L‐type calcium channel agonist, to induce a contraction. Inhibition of the BayK8644‐induced contraction was demonstrated after a 60 min incubation with 10 −5 M and 10 −4 M 2ME. Our results suggest that 2ME decreases coronary arterial tone by inhibition of calcium influx. Support: NCRR of the NIH, Grant# P20 RR‐16460.