| Objective: To study the effects of isosorbide-5-monon~ itrate (ISMN) on the sympathetic purinergic vasoconstriction induced by electric field stimulation, and the possible mechanism.Method: Isometric vasoconstriction of the rabbit saphenous arterial rings and the vasoconstrictive responses to electric field stimulation were recorded.Results: The vasoconstrictive responses to electric field stimulation (15V, 1ms pulse duration, 2-16Hz) were frequency-dependant in the rabbit saphenous arterial rings. Tetrodotoxin (TTX, 0.1 u M) abolished all of the contractions. An a ,-adrenoceptor antagonist prazosin (Pra, 1 u M) reduced the neurogenic contractions at 16Hz partially but not significantly, and it did not affect the vascular responses to other frequencies (2-8Hz). After the treatment of a combination of desensitizing the P2X] receptors with a , |3 -methylene ATP (a , ?-meATP, 3 u M) and using Pra (1 u M), all contractions induced by electric stimulation were abolished. In the preparations pre-contracted with noradrenaline (NA), single concertration of ISMN at 0.3mMor l.OmM produced a vasodilatation by a 12% or 22%, but not at 0.1 mM. However, repeated administrations of ISMN several times to the arterial preparations induced an obvious tolerance to the drug. ISMN given in the manner of one concentration to one preparation significantly inhibited the contractions induced by electric stimulation at 8Hz at O.lmM, ISMN at 0.3mM reduced the contractions induced by electric stimulation at 2-16Hz. The highest concentration of ISMN (l.OmM) significantly reduced the contractions by 46% (2Hz), 47% (4Hz), 34% (8Hz) and 22% (16Hz). ISMN(0.3-l.OmM) did not affect the vascular responses to exogenous NA (0.01-100 U M) and adenosine triphosphate (ImM).Conclusion: ISMN significantly inhibited the purinergic vasoconstrictions induced by sympathetic nerve stimulation via both prejunctional and postjunctional mechanisms.
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