Electrochemical and electrophysiological characterization of neurotransmitter release from sympathetic nerves supplying rat mesenteric arteries

Abstract

1 Characteristic features of noradrenaline (NA) and adenosine 5'-triphosphate (ATP) release from postganglionic sympathetic nerves in rat small mesenteric arteries in vitro have been investigated on an impulse-by-impulse basis. NA release was measured using continuous amperometry and ATP release was monitored by intracellular recording of excitatory junction potentials (e.j.ps). 2 Electrical stimuli evoked transient increases in oxidation current. During trains of ten stimuli at 0.5 ± 4 Hz there was a depression in the amplitude of oxidation currents evoked following the ®rst stimulus in the train. 3 The neuronal NA uptake inhibitor, desmethylimipramine (1 mM), increased the amplitude of the summed oxidation current evoked by ten stimuli at 1 Hz and slowed the decay of oxidation currents evoked by trains of ten stimuli at 1 and 10 Hz. 4 The a 2 -adrenoceptor antagonist, idazoxan (1 mM), increased the amplitudes of the oxidation currents evoked during trains of ten stimuli at 0.5 ± 10 Hz but had no eect on the oxidation currents evoked by the ®rst stimulus in the train. 5 Idazoxan (1 mM) increased the amplitude of all e.j.ps evoked during trains of stimuli at 0.5 and 1 Hz. In addition, the facilitatory eect of idazoxan on e.j.ps was signi®cantly greater than that on oxidation currents. 6 The ®ndings indicate that NA release from sympathetic nerves supplying small mesenteric arteries is regulated by activation of presynaptic a 2 -adrenoceptors and that clearance of released NA in this tissue depends, in part, upon neuronal uptake. The dierent eects of idazoxan on the oxidation currents and e.j.ps may indicate that the release of NA and ATP is dierentially modulated.

Selective Increase in Renal Arcuate Innervation Density and Neurogenic Constriction in Chronic Angiotensin II-Infused Rats

“…[23][24][25][26][27][28][29] The density of neuromuscular junctions was not increased by Ang II, suggesting that increases in ATP release are unlikely to be the cause of the increased sensitivity of the renal arcuate arteries to nerve stimulation after treatment. However, the low incidence of neuromuscular junctions and the possibility of a diffuse distribution of purinoceptors mean that this conclusion is made cautiously.…”

“…We used morphological 12 and functional approaches and also studied a similar size artery from a non-renal systemic vascular bed, namely the wellcharacterized mesenteric artery. 6,7,17,24 The pump delivered either vehicle (0.9% NaCl containing heparin 10 IU/mL, nϭ21) or Ang II (10 ng/kg per minute, nϭ21), a dose that had negligible pressor effects (Ͻ3 mm Hg in preliminary experiments) when administered acutely. All experiments were conducted in accordance with the Australian Code of Practice for the Care and Use of Animals for Scientific Purposes.…”

Properties of the Venous and Arterial Innervation in the Mesentery.

“…The saphenous artery and vein are innervated by separate sympathetic paravertebral ganglionic neurons (Dehal et al, 1992), suggesting that this may be a general property of sympathetic vascular innervation. Indeed organ-specific innervation by sympathetic neurons has been demonstrated for several ganglia (Andrews et al, 1996;Dunn et al, 1999).…”

“…After its secretion into the junctional region approximately 95% of the secreted norepinephrine is transported into the nerve terminal via the norepinephrine transporter (Axelrod and Kopin, 1969); the remainder of the norepinephrine is either transported into smooth muscle, metabolized by enzymes or diffuses from the junction. If the activity of the transporter is reduced by selective antagonists, more norepinephrine persists in the junction with the result that there is a larger response in the vascular smooth muscle (depolarization/contraction) (Dunn et al, 1999). The major inactivation mechanism for released ATP is through enzymatic degradation by a soluble nucleotidase that is released with ATP from the nerve terminals (Todorov et al, 1997).…”

“…Both mRNA and protein can be isolated from extracts of mesenteric artery and vein as well as of sympathetic ganglia. When the transporter is blocked with cocaine or the tricyclic antidepressant desmethylimipramine there is an increase in norepinephrine in the junctional cleft and enhanced vasoconstriction (Dunn et al, 1999).…”