Existence of different α₁‐adrenoceptor subtypes in junctional and extrajunctional neurovascular regions in canine splenic arteries

Abstract

1 The present study attempted to characterize the a 1 -adrenoceptor subtypes mediating vasoconstrictor responses to administered and nerve stimulation-evoked noradrenaline (NA) release in the isolated and perfused canine splenic artery. 2 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 a 1 -adrenoceptor-mediated response in the canine splenic artery. 3 The eects of a 1 -adrenoceptor subtype antagonists on neuronally-mediated second peaked vasoconstrictions were analysed. BMY 7378 (10 ± 100 nM), a selective a 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 mM), a selective a 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 a 1A -adrenoceptor antagonist potentiated nerve-stimulationevoked double peaked vasoconstrictions, especially at low frequencies (1 and 4 Hz). 4 Vasoconstrictor responses to administered NA were dose-dependently antagonized by WB 4101 (10 ± 100 nM), but were not signi®cantly aected by either BMY 7378 (10 ± 100 nM) or by CEC (60 mM). 5 The present results indicate that NA released from sympathetic nerves may junctionally exert its vasoconstrictor eect via activation of postjunctional a 1B -and in part a 1D -adrenoceptors, whereas exogenous NA extrajunctionally activates a 1A -adrenoceptors to produce its vascular action in canine splenic arteries.

Differences in α1-Adrenoceptor Subtype-Mediated Vasoconstriction by Tyramine and Nerve Stimulation in Canine Splenic Artery

“…It was demonstrated that the neurogenic second peaked response was much reduced by chloroethylclonidine and was partially inhibited by BMY 7378, but was not affected by WB 4101 (8,9), as confirmed even in the present study. However, there is possibility that chloroethylclonidine inhibits the PNS-induced response by activating the α 2 -adrenoceptors in sympathetic nerve terminals (27).…”

“…The sympathetic-innervated subtypes of junctional α 1 -adrenoceptors in the canine splenic artery have been shown to be mainly α 1B -, and in part, α 1D -subtype, rather than the α 1A -subtype (8,9,21). It was demonstrated that the neurogenic second peaked response was much reduced by chloroethylclonidine and was partially inhibited by BMY 7378, but was not affected by WB 4101 (8,9), as confirmed even in the present study.…”

“…On the other hand, the vasoconstrictor response to administered noradrenaline was antagonized by WB 4101, whereas they were not inhibited by either chloroethylclonidine or BMY 7378 (8,9). It is therefore hypothesized that α 1B -, and α 1D -adrenoceptors may be located in the junctional region, whereas α 1A -adrenoceptors may reside in the extrajunctional region of the neuroeffector junction in the canine splenic artery (8,21,29).…”

“…It is therefore hypothesized that α 1B -, and α 1D -adrenoceptors may be located in the junctional region, whereas α 1A -adrenoceptors may reside in the extrajunctional region of the neuroeffector junction in the canine splenic artery (8,21,29). Tyramine is recognized to activate the postjunctional α-adrenoceptors in sympathetically innervated tissues by releasing intraneuronally stored noradrenaline into the junctional cleft (1 -4).…”

“…The α 1B -adrenoceptor subtype is demonstrated to be critical in sympathetically mediated vasoconstriction and involved in the control of blood pressure (10,11). Studies on the canine splenic artery have indicated that the postjunctional α 1B -and in part α 1D -adrenoceptor subtypes received a sympathetic adrenergic innervation, whereas the extrajunctionally located α 1A -adrenoceptor was activated by exogenously administered noradrenaline (8,9). In the canine splenic artery, α 1 -adrenoceptors have been identified to be a functional subtype in mediating vasoconstriction in response to tyramine (12).…”