Existence of different alpha(1)-adrenoceptor subtypes in junctional and extrajunctional neurovascular regions in canine splenic arteries.
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ABSTRACT: The present study attempted to characterize the alpha(1)-adrenoceptor subtypes mediating vasoconstrictor responses to administered and nerve stimulation-evoked noradrenaline (NA) release in the isolated and perfused canine splenic artery. A previous study demonstrated that periarterial electrical nerve stimulation (30 s trains of pulses at a frequency of 1, 4 or 10 Hz) induced a double peaked vasoconstriction consisting of an initial transient, predominantly P2X-purinoceptor-mediated constriction followed by a prolonged, mainly alpha(1)-adrenoceptor-mediated response in the canine splenic artery. The effects of alpha(1)-adrenoceptor subtype antagonists on neuronally-mediated second peaked vasoconstrictions were analysed. BMY 7378 (10 - 100 nM), a selective alpha(1D)-adrenoceptor antagonist produced a dose-dependent inhibition of the second peak responses at all frequencies used. BMY 7378 (100 nM) reduced these responses by approximately 30%. Exposure of tissues to chloroethylclonidine (CEC, 60 microM), a selective alpha(1B)-adrenoceptor antagonist attenuated the second peak response by approximately 60%, even in the presence of BMY 7378 (100 nM). On the other hand, WB 4101 (100 nM), a selective alpha(1A)-adrenoceptor antagonist potentiated nerve-stimulation-evoked double peaked vasoconstrictions, especially at low frequencies (1 and 4 Hz). Vasoconstrictor responses to administered NA were dose-dependently antagonized by WB 4101 (10 - 100 nM), but were not significantly affected by either BMY 7378 (10 - 100 nM) or by CEC (60 microM). The present results indicate that NA released from sympathetic nerves may junctionally exert its vasoconstrictor effect via activation of postjunctional alpha(1B)- and in part alpha(1D)-adrenoceptors, whereas exogenous NA extrajunctionally activates alpha(1A)-adrenoceptors to produce its vascular action in canine splenic arteries.
SUBMITTER: Yang XP
PROVIDER: S-EPMC1572737 | biostudies-other | 2001 Apr
REPOSITORIES: biostudies-other
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