Effects of omega-conotoxin GVIA and diltiazem on double peaked vasoconstrictor responses to periarterial electric nerve stimulation in isolated canine splenic artery.
The actions of omega-conotoxin (omega-CTX) and diltiazem on adrenergic and purinergic components of double peaked vasoconstrictor responses to periarterial nerve stimulation have been investigated in the isolated, perfused canine splenic arterial preparation. Double peaked vasoconstrictions (biphases of vasoconstrictors) were consistently observed in the conditions of 30 s trains of pulses at 1 - 10 Hz frequencies. omega-CTX (1 - 30 nM) produced similar inhibitory effects on the first phase and second phase responses in a dose-related manner. Thirty nM omega-CTX almost completely inhibited the biphasic vasoconstrictions at any used frequencies but did not affect the vasoconstrictor responses to exogenous applied ATP (0.01 - 1 micromol) and noradrenaline (0.03 - 3 nmol). Intraluminal application of a large dose of diltiazem (3 - 10 microM) also produced a dose-dependent inhibitory effect on biphasic vasoconstrictions at any used frequencies. Three microM diltiazem exerted rather a larger inhibitory effect on the second phase than the first phase response at low frequencies (1 - 3 Hz), but a similar inhibition on first and second phasic responses at high frequencies (6 - 10 Hz). An extremely high dose of diltiazem (10 microM) almost completely inhibited the biphasic vasoconstrictor responses to nerve stimulation, and slightly inhibited the contractile responses to exogenous applied ATP (0.01 - 1 micromol) and noradrenaline (0.03 - 3 nmol). The present results indicate that omega-CTX selectively acts prejunctionally to inhibit the release of transmitters from sympathetic nerve terminals, and omega-CTX-sensitive calcium channels may produce a parallel controlling of purinergic and adrenergic components of sympathetic cotransmission. A large dose of diltiazem has inhibitory effects on both prejunctional and postjunctional sympathetic co-transmission. British Journal of Pharmacology (2000) 129, 47 - 52
Yang
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Department of Pharmacology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
Chiba
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D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects; D020864:Calcium Channels, N-Type / Q000187:drug effects; D004110:Diltiazem / Q000494:pharmacology*; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009411:Nerve Endings / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology; D013157:Splenic Artery / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D011983:Receptors, Purinergic; D014662:Vasoconstrictor Agents; D000255:Adenosine Triphosphate; D020866:omega-Conotoxin GVIA; D004110:Diltiazem; D009638:Norepinephrine