Sympathetic Neurovascular Transmission in the Mouse Tail Artery

Stevenson, C., Daly, C. , McLachlan, E. and McGrath, I. (2012) Sympathetic Neurovascular Transmission in the Mouse Tail Artery. Physiology 2012, Edinburgh, UK, 02-05 Jul 2012.

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Publisher's URL: https://www.physoc.org/abstracts/sympathetic-neurovascular-transmission-in-the-mouse-tail-artery/

Abstract

In order to analyse the postjunctional mechanisms involved in sympathetic neurovascular transmission, we are developing transgenic mice, particularly α1-AR knockouts. The first step, however, is to define neurovascular transmission in the tail artery of normal mice using pharmacological antagonists, as has been done for the rat. Perivascular stimulation of rat tail artery evokes depolarizations mediated by ATP and noradrenaline (1) but contraction is mediated largely by α1- and α2-adrenoceptors (ARs), probably acting synergistically (2). In vivo, α2- but not α1-AR blockers cause profound vasodilation, increasing tail skin temperature (3). The α2-AR-mediated effects are more readily shown distally (4). Further, activation of capsaicin-sensitive peptidergic afferent nerves, present in small numbers around the rat tail artery (5), can elicit relaxation. Male C57Bl mice (4-6 months) were killed with CO2. Ring segments of the tail artery 2mm long were prepared from proximal (2cm) and distal (5cm) sites. Vessels were mounted on a wire myograph in oxygenated physiological saline at 37oC. Responses to 62.5mM KCl were recorded. Vessels were incubated for 30 minutes in 1 µM capsaicin to block release of calcitonin gene-related peptide from afferent nerves. Frequency response curves (FRC) to maximal stimuli were constructed before and after capsaicin (0.5Hz-8Hz; 20 pulses; 0.3ms pulse width; 20V) and in the presence of various combinations of 100nM prazosin (α1-AR antagonist), 100nM rauwolscine (α2-AR antagonist), and 1mM suramin (P2X receptor antagonist). Data were analysed using unpaired and paired t-tests as well as one way ANOVA with Bonferroni’s post-hoc test. Capsaicin induced relaxation if vessel tone was raised, but caused no change in responses to nerve stimulation at either location (P>0.05, n=23, proximal; n=6, distal). However, responses in proximal segments at high frequencies were significantly greater than for distal segments after, but not before, capsaicin. In proximal segments, prazosin reduced responses at all frequencies by ~40% (P<0.05, n=6, one way ANOVA). Rauwolscine also reduced responses, exerting more effect at 0.5Hz (~80% block) than at 8Hz (~30% block). Suramin alone reduced responses at each frequency by ~40%. In distal segments, neither prazosin nor suramin significantly reduced the responses, which were virtually abolished by rauwolscine. While both α1- and α2-ARs are involved in nerve evoked contraction of the proximal mouse tail artery, contractile responses mediated by α2-ARs dominate at low stimulation frequencies, especially in the distal part. Unlike in the rat tail artery, the contribution of P2X receptors to nerve evoked contraction is substantial and will be clarified in mice that lack alpha-adrenoceptors.

Item Type:Conference or Workshop Item
Additional Information:Poster Communication.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McLachlan, Professor Elspeth and Daly, Professor Craig and McGrath, Miss Isla
Authors: Stevenson, C., Daly, C., McLachlan, E., and McGrath, I.
College/School:College of Medical Veterinary and Life Sciences > School of Life Sciences

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