Effects of YMⅢ on vascular contractive activities and the underlying mechanism / 中国药理学通报

ABSTRACT

Aim To investigate the effects of YMⅢ,a derivative of naftopidil, on the vascular contractive activities in rabbit aorta and to explore its vasodilative mechanisms.Methods The isotonic contractions of the thoracic aorta strips from rabbits were recorded, and the effects of YMⅢ on the concentration-response curves of noradrenaline(NA),high potassium and 5-hydroxytryptamine(5-HT)were observed.Intracellular free Ca2+([Ca2+]i)was investigated in the pressence of and the absence of YMⅢ in different conditions.Results YMⅢ(10-8,5?10-8,10-7 mol?L-1)shifted the concentration-response curve of NA with a parallel manner to right, the maximum response was unchanged and the pA2 value was 8.00; YMⅢ (10-5 mol?L-1)also shifted the concentration-response curve induced by high potassium to right but with non-parallel manner,the response was depressed and the pD′2 value was 4.26. However, YMⅢ(10-7,10-6,10-5 mol?L-1)had no statistical influence on the concentration-response curve induced by 5-HT, although it tended to depress the response of the curve at 10-5 mol?L-1.In Ca2+-free medium,YMⅢ (10-8,5?10-8 and 10-7mol?L-1) significantly inhibited the transient contraction induced by NA and the long-lasting one induced by addition of Ca2+ with a concentration-dependent manner.But even at 10-5 mol?L-1,it did not inhibit the contraction induced by caffeine.Conclusions YMⅢ may be ?-adrenergic receptor blocker.Its vasodilative mechanism may be related toblocking ?-adrenergic receptor on cell membrane resulting in the inhibition on the influx of extracellular Ca2+ and the release of intracellular calcium.