Genistein inhibits contractile force, intracellularCa2+ increase and Ca2+ oscillations induced byserotonin in rat aortic smooth muscle

ABSTRACT

The soy-derived isoflavones genistein and daidzein affect the contractile state ofdifferent kinds of smooth muscle. We describe acute effects of genistein and daidzeinon contractile force and intracellular Ca2+ concentration ([Ca2+]i) in in situ smoothmuscle of rat aorta. Serotonin (5-HT) (2 ìM) or a depolarizing high K+ solution producedthe contraction of aortic rings, which were immediately relaxed by 20 ìMgenistein and by 20 ìM daidzein. Accordingly, both 5-HT and a high K+ solutionincreased the [Ca2+]i in in situ smooth muscle cells. Genistein strongly inhibited the[Ca2+]i increase evoked by 5-HT (74.0 ± 7.3%, n=11, p<0.05), and had a smallereffect on high K+ induced [Ca2+]i increase (19.9 ± 4.0%, n=7, p<0.05). The K+ channelsblocker tetraethylammonium (TEA) (0.5 mM) diminished genistein effects on 5-HT-induced [Ca2+]i increase. Interestingly, during prolonged application of 5-HT,the [Ca2+]i oscillated and a short (90 s) preincubation with genistein (20 ìM) significantlydiminished the frequency of the oscillations. This effect was totally abolishedby TEA. In conclusion, in rat aortic smooth muscle, genistein is capable of diminishingthe increase in [Ca2+]i and in force evoked by 5-HT and high K+ solution, andof decreasing the frequency of [Ca2+]i oscillations induced by 5-HT. The short timerequired by genistein, and the relaxing effect of daidzein suggest that tyrosine kinasesinhibition is not involved. The small inhibiting effect of genistein on the [Ca2+]iincrease evoked by high K+ and the effect of TEA point to the activation by genisteinof calcium-activated K+ channels (AU)

RESUMEN

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