Effects of tetrodotoxin on biphasic vasoconstrictive responses to electric stimulation in rabbit saphenous artery / 中国药理学通报

ABSTRACT

Aim To establish a model of biphasic vasoconstriction induced by electrical stimulation, and analyze effects of 1～100 nmol?L~(-1) tetrodotoxin (TTX) on the biphasic vasoconstriction in the ring preparation of the rabbit saphenous artery. Methods Isometric vasoconstriction of the rabbit saphenous arterial rings was recorded, and the sympathetic nerves of the arterial rings were activated with electrical stimulation. Results The biphasic neurogenic vasoconstriction was consistently induced by electrical stimulation (15 V,1 ms pulse duration,2～16 Hz for 32 s) in a frequency-related manner in the rabbit saphenous artery. TTX (3 nmol?L~(-1)),a neuronally selective sodium channel blocker,did not affect the first phase of vasoconstriction,but it markedly inhibited the second phase of vasoconstrictive responses to 2～16 Hz stimulation by 44 %～67 %. Increasing the concentration of TTX to 10 nmol?L~(-1), TTX inhibited the first phase of the vasocontractive responses to 4～16 Hz stimulation by 40%～57%,whereas it inhibited more than 90% of the second phase of vasoconstriction. Concentration-response curves for NA(0.01～30 ?mol?L~(-1)) were not affected by TTX (0.1 ?mol?L~(-1)), but the same concentration of TTX completely inhibited the biphasic vascular responses to electrical stimulation. The biphasic contractile responses to electrical stimulation were all abolished by guanethidine (10 ?mol?L~(-1)), but the vasoconstrictive responses to exogenous NA were not affected by it. Conclusion Biphasic vasoconstriction can be induced by electrical stimulation,and the first and the second phases of vasoconstriction are mediated by neurotransmitters released from sympathetic nerves in the rabbit isolated saphenous arterial ring preparation.