Modulation of vascular reactivity by kaempferol in porcine coronary arteries

Abstract

Kaempferol is one of the major bioactive components of the Chinese herbal medicine, Carthamus tinctorius, which has long been used for the management of various cardiovascular diseases. The present study aimed to examine the vascular effects of kaempferol and to investigate the mechanism through which kaempferol modulated vascular reactivity. In the presence of indomethacin, kaempferol directly relaxed porcine coronary arteries with and without endothelium at high concentrations. At lower concentration, kaempferol reduced contractions to the depolarizing agent potassium chloride and the thromboxane A2 analogue U46619, and poten- tiated relaxation to SNP. The potentiating effect of kaempferol on SNPinduced relaxation was partially inhibited by the big conductance calciumactivated potassium channel (BKCa) blocker, iberiotoxin, but not by the selective intermediate conductance calcium-activated potassium (KCa) channel blocker TRAM-34 and small conductance KCa channel blocker UCL-1684, in porcine coronary arteries with and without endothelium. On the other hand, iberiotoxin did not affect the inhibitory effect of kaempferol on contractions. The big and intermediate conductance KCa channel blocker charybdotoxin or the protein kinase A blocker KT5720 were also without effect. Neither iberiotoxin, charybdotoxin, KT5720 nor the nitric oxide synthase inhibitor L-NAME affected the direct relaxation of high concentrations of kaempferol. These findings suggest that kaempferol potentiates relaxation to SNP partly through activation of big conductance KCa channels in vascular smooth muscle. However, other mechanisms are involved in the direct relaxation effect and the inhibitory effect on contraction of kaempferol in porcine coronary arteries.