BACKGROUND
We are developing transgenic mice, particularly α1-AR knockouts, to analyse postjunctional mechanisms involved in sympathetic neurovascular transmission. First we need to define neurovascular transmission in normal mice using pharmacological antagonists, as has been done for rat vessels. Perivascular stimulation of rat tail artery evokes depolarizations mediated by ATP and noradrenaline1 but contractions mediated by α1- and α2-adrenoceptors (ARs), probably acting synergistically2 . In vivo, α2- but not α1-AR blockers cause vasodilation, increasing tail skin temperature3 and α2-AR-mediated effects are more prominent distally4 .
METHODS
Male C57Bl mice (4-6 months) were killed with CO2. Arterial rings 2 mm long from proximal (2 cm) and distal (5 cm) sites along the tail (~8 cm long) were mounted on myographs. The effects of 100 nM prazosin (α1-AR antagonist), 100 nM rauwolscine (α2-AR antagonist) and 1 mM suramin (P2X receptor antagonist) on contractile responses to supramaximal transmural stimuli (20 V; 0.3 ms pulse width; 0.5 Hz-8 Hz; 20 pulses) were examined.
RESULTS
Peak amplitude of contractions occurred earlier at higher frequencies and were larger proximally. Three components of contraction were identified. Prazosin reduced the early phase of contraction by ~50% at both sites whereas rauwolscine reduced the later phase, exerting more block at 0.5 Hz (~80%) than at 8 Hz (~50%). Suramin reduced both phases of contraction distally by ~40%, but potentiated the later phase proximally.
CONCLUSIONS
P2X receptors and α1- and α2-ARs are involved in nerve-evoked contractions of mouse tail artery, with responses mediated by α2-ARs dominating at lower frequencies, especially in the distal artery. Unlike in rat, P2X receptor activation inhibits the α2-AR component in the proximal segment but potentiates it distally. The use of transgenic mice will clarify the selectivity of antagonists and these components of nerve-mediated contraction.
DISCLOSURE
None of the authors has a conflict of interest.