PURINERGIC and ADRENERGIC COTRANSMISSION IN CANINE ISOLATED and PERFUSED GASTROEPIPLOIC ARTERIES

Abstract

1. The vasoconstrictor responses of canine gastroepiploic artery to periarterial electrical nerve stimulation (PNS; 30 s trains of pulses at a frequency of 2, 4 or 8 Hz) were observed in a frequency dependent manner. The PNS-induced vasoconstrictions were abolished by tetrodotoxin (1 micromol/L) and mostly depressed but not completely by guanethidine (10 micromol/L). 2. Vasoconstrictor responses to administered noradrenaline were antagonized significantly by prazosin (0.1 micromol/L), an alpha1-adrenoceptor antagonist, but were not significantly affected by suramin (100 micromol/L), a P2 purinoceptor antagonist, or alpha,beta-methylene ATP (1 micromol/L), a P2X receptor desensitizing agent. Exogenous ATP-induced responses were clearly depressed by suramin or alpha,beta-methylene ATP, but were not significantly affected by prazosin. 3. The vasoconstrictor responses to PNS at a low frequency (2 and 4 Hz) of stimulation were markedly inhibited by suramin (100 micromol/L) and by alpha,beta-methylene ATP (1 micromol/L). The remaining responses after suramin or alpha,beta-methylene ATP were abolished by subsequent application of prazosin (0.1 micromol/L). At a high frequency (8 Hz) of stimulation, the vascular response was not significantly inhibited by suramin or alpha,beta-methylene ATP, but it was abolished by prazosin. 4. Injection of xylazine (0.3-30 nmol/L), an alpha2-adrenoceptor agonist, did not induce any clear vasoconstriction. The exposure of tissues to rauwolscine (0.1-0.3 micromol/L), an alpha2-adrenoceptor antagonist, dose-dependently increased PNS-induced vasoconstrictions at all frequencies tested. 5. The present results indicate that ATP acts as a cotransmitter with noradrenaline and is responsible for post-junctional vasoconstrictor responses at low frequencies of sitmulation, whereas the effect of noradrenaline is dominant at high-frequency stimulation in canine gastroepiploic artery. Prejunctional alpha2-adrenoceptor autoinhibition may modulate the release of either noradrenaline or ATP from sympathetic nerve terminals.

Neurogenic double‐peaked vasoconstriction of human gastroepiploic artery is mediated by both α1‐ and α2‐adrenoceptors

“…The present study provided further evidence that the neurogenic vasoconstriction of the human gastroepiploic artery is adrenergic in origin, since the neurogenic responses were not significantly affected by a,b-methylene ATP, a P2X-receptor desensitizing agent, but were readily blocked by phentolamine, an a-adrenoceptor antagonist. In contrast, a purinergic component was partially involved in mediating neuronal responses in the canine gastroepiploic artery (Tanaka et al, 2003). This evidence suggests that the contribution of each component of cotransmission to neuroeffector constriction varies between different species, and there are also tissue differences.…”

Is tonic sympathetic vasoconstriction increased in the skeletal muscle vasculature of aged canines?

“…However, it is now recognized that NE also binds to postsynaptic ␣2-receptors and that the nonadrenergic neurotransmitters ATP and NPY contribute to sympathetic vasoconstriction through binding with purinergic (P 2x ) and neuropeptide Y (NPY) receptors on vascular smooth muscle (2, 4 -7, 10, 20 -22, 34, 35, 46, 51, 52, 54, 55). The type, pattern, and quantity of neurotransmitter released are sensitive to the frequency of neuron firing (2,20,22,34,35,46,54,55). In particular, low-discharge frequencies favor ATP release followed by NE, whereas midrange discharge frequencies produce both ATP and NE release, and high discharge frequencies favor NPY release (21,34,46,51).…”

Purinergic receptors in the splanchnic circulation

“…As previously pointed out, the majority of the studies show that low frequencies of stimulation favour purinergic neurotransmission while high frequencies promote adrenergic neurotransmission [142,143,187,192]. A variation was found in the canine gastroepiploic [170] and splenic artery [192]. In these preparations, the first phase is mediated by P2X receptors at low frequencies of stimulation, but also presynaptic α-adrenoceptors at high frequencies, while the second phase response involves mostly α 1 -adrenoceptors and partially P2X receptor activations at all frequencies used.…”

“…In what concerns the splanchnic circulation, the first description of such corelease was reported by Su [164] in the rabbit portal vein. Since then, growing evidence emerged that ATP is a cotransmitter in the splanchnic circulation of the dog [9,94,113,114,144,170], rabbit [140,181], guinea-pig [8], and rat [19,37,44].…”