Mechanism of the antihypertensive and vasorelaxant effects of the flavonoid tiliroside in resistance arteries
2013
Hypertension is a leading cause of death and disability globally, and its
prevalence continues to accelerate. The cardiovascular effects of the
flavonoid tiliroside have never been reported. In this work, using
complementary in vivo and in vitro approaches, we describe the
antihypertensive effect of tiliroside and the underlying mechanisms involved
in the reduction of blood pressure. Tiliroside (1, 5 or 10 mg/kg) induced a
dose-dependent long-lasting decrease in blood pressure in conscious
DOCA-salt hypertensive rats that was accompanied by an increased heart rate.
Tiliroside also induced a concentration-dependent vasodilation of mesenteric
resistance arteries precontracted with phenylephrine. Removal of the
endothelium or pretreatment of the preparation with L-NAME or indomethacin
did not modify the vasodilator response for tiliroside. When vessels were
precontracted with a high K + (50 mM) solution, tiliroside
exhibited a vasodilator effect similar to that observed in vessels
precontracted with phenylephrine. Experiments carried out in nominally
Ca 2+ -free solution showed that tiliroside antagonized
CaCl 2 -induced contractions. Moreover, tiliroside reduced the
rise in intracellular Ca 2+ concentration induced by membrane
depolarization in vascular smooth muscle cells. Finally, tiliroside
decreased the voltage-activated peak amplitude of the L-type Ca 2+ channel current in freshly dissociated vascular smooth muscle cells from
mesenteric arteries. Altogether, our results point to an antihypertensive
effect of tiliroside due to a reduction in peripheral resistance through
blockage of voltage-activated peak amplitude of the L-type Ca 2+ channel in smooth muscle cells.
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