Abstract
The present study characterized the mechanisms involved in the vasodilator
effect of two mono-oxygenated xanthones, 4-hydroxyxanthone and
4-methoxyxanthone. 9-Xanthenone, the base structure of xanthones, was used
for comparison. 4-Hydroxyxanthone and 9-xanthenone induced a
concentration-dependent and endothelium-independent vasodilator effect in
arteries precontracted with phenylephrine (0.1 µmol · L−1) or KCl
(50 mmol · L−1). 4-Methoxyxanthone induced a
concentration-dependent vasodilator effect in arteries precontracted with
phenylephrine, which was partially endothelium-dependent, and involved
production of nitric oxide. In endothelium-denuded arteries precontracted
with KCl, the vasodilator effect of 4-methoxyxanthone was abolished. The
vasodilator effect of 4-hydroxyxanthone (96.22 ± 2.10 %) and
4-methoxyxanthone (96.57 ± 12.40 %) was significantly higher than observed
with 9-xanthenone (53.63 ± 8.31 %). The presence of an oxygenated radical in
position 4 made 4-hydroxyxanthone (pIC50 = 4.45 ± 0.07) and
4-methoxyxanthone (pIC50 = 5.04 ± 0.09) more potent as a
vasodilator than 9-xanthenone (pIC50 = 3.92 ± 0.16). In addition,
4-methoxyxanthone was more potent than the other two xanthones.
Ca2+ transients in vascular smooth muscle cells elicited by
high K+ were abolished by 4-hydroxyxanthone and 9-xanthenone. The
endothelium-independent effect of 4-methoxyxanthone was abolished by
inhibition of K+ channels by tetraethylammonium. The current work
shows that an oxygenated group in position 4 is essential to achieve
Emax and to increase the potency of xanthones as
vasodilators. Substitution of an OH by OCH3 in position 4
increases the potency of the vasodilator effect and changes the underling
mechanism of action from the blockade of L-type calcium channels to an
increase in NO production and activation of K+ channels.
Key words
xanthones - 4-hydroxyxanthone - 4-methoxyxanthone - vasodilation - Ca
2+ channels - nitric oxide - K
+ channels
