Effects of phytoestrogens on acetylcholine- and isoprenaline-induced vasodilation in rat aorta.

The influence of the phytoestrogen, isoflavones, on vasodilating responses of the thoracic aorta precontracted with norepinephrine, together with the stimulatory effect on uterine weight (uterotrophic effect), was investigated in ovariectomized rats. In comparison with intact rats, acetylcholine (ACh)-induced vasodilation showed a tendency to be decreased by ovariectomy. On the other hand, isoprenaline (ISO)-induced vasodilation was significantly increased by ovariectomy. Estrogen replacement (17beta-estradiol dipropionate, 300 microg/kg per week, for 1 month) completely restored the impaired ACh- and ISO-induced vasodilation caused by ovariectomy. Dietary isoflavone aglycones (containing 52% genistein, 42% daidzein and 6% glycitein) of 157 mg/kg per day (not 67 mg/kg per day) for 1 month, in addition to the effects of estrogen replacement, completely restored the impaired vasodilation caused by ovariectomy. However, the uterotrophic effect of dietary isoflavones of 157 mg/kg per day was incomplete as compared with that by estrogen replacement. These results indicate that phytoestrogen, isoflavones, certainly possess estrogenic actions on the vasodilating responses caused by ACh and ISO, as well as a weaker uterotrophic effect.

Effects of pimobendan, a new cardiotonic agent, on contractile responses in single skeletal muscle fibres of the frog.

Effects of a new cardiotonic agent, pimobendan, on contraction were investigated in single intact skeletal muscle fibres of the frog. Pimobendan increased twitch tension in a concentration-dependent manner regardless of the presence or absence of Ca2+ without any effect on tetanic tension, the resting membrane potential and the shape of the action potential. Pimobendan caused a further increase in twitch tension potentiated by caffeine (1 mM). Adenine, an inhibitor of Ca2+-induced Ca2+ release from the sarcoplasmic reticulum, inhibited twitch tension potentiated by caffeine but not by pimobendan, suggesting that twitch potentiation by pimobendan is not attributed to increases in Ca2+-induced Ca2+ release. Pimobendan failed to increase cAMP levels in the skeletal muscle, though forskolin significantly increased it without any effect on twitch tension. Contractile responses to high concentrations of caffeine and K+ were also potentiated by pimobendan. These results suggest that the potentiating effect of pimobendan on skeletal muscle contraction is mainly due to the increase in Ca2+ sensitivity to the contractile apparatus.