Description:
Abnormal coronary blood flow is associated with inhibition of Ca2+‐activated K+ (BK) channels and/or stimulation of voltage‐gated Ca2+ channels. Our lab previously demonstrated that the estrogen metabolite, 2‐methoxyestradiol (2‐MeOH) inhibits Ca2+‐dependent contractions. The objective of this study was to determine if 2‐MeOH can induce vasodilation via BK channels. This study used right coronary arteries from hearts obtained from female pigs. The arteries were cut into 4 mm rings to measure isometric tension in response to a depolarizing KCl solution. The rings were exposed to 2‐MeOH (10 nM to 10 μM) or its vehicle (ethanol) in the presence and absence of the BK blocker, tetraethylammonium (TEA, 1 mM). Physiological [2‐MeOH] increased the KCl‐induced contraction in the presence of TEA by 2‐fold. Coronary arteries were also cut into longitudinal strips to determine BK protein expression using Western blots. The strips were incubated (37°C at 5% CO2) for 24 hrs in 2‐MeOH (10 nM to 1 μM) or ethanol. Densitometric analyses of the blots indicate that 2‐MeOH increased BK channel expression greater than 2‐fold. Data from our study indicate that physiological concentrations of 2‐MeOH induce vasodilation by increasing the protein expression of the BK channel. Support: NCRR of the NIH, Grant #P20 RR‐16460.