Transmitter characteristics of small mesenteric arteries from the rat

Abstract

We have studied the neurogenic response of small mesenteric arteries from the rat to evaluate the involvement of possible co-transmitters under various modes of stimulation. Segments of small branches of the mesenteric artery were mounted in a myograph and the intramural nerves were activated with transmural electrical stimulation. A single stimulation of the nerves caused a contraction that was reduced by only 20% in the presence of adrenergic blocking agents (prazosin or phenoxybenzamine), whereas the steady-state response to continuous nerve stimulation of high frequency was reduced by 90-95%. In contrast, all responses to applied noradrenaline in doses up to at least 1 mM were eliminated by phenoxybenzamine treatment. The stable ATP analogue, alpha,beta-methylene ATP, reduced the response to a single nerve stimulation by 70%, but reduced the contraction caused by continuous high-frequency nerve stimulation by only 10%. None of these agents affected the response to applied neuropeptide Y (NPY). The response of relaxed vessels to nerve stimulation was totally blocked by the combination of an adrenoceptor-blocking agent and alpha,beta-methylene ATP, although even in this situation a further neurogenic response could be revealed in vessels precontracted with vasopressin. Responses to either single stimuli or brief burst stimulations were potentiated after high-frequency stimulation. Both the adrenergic and non-adrenergic components were enhanced to roughly the same extent. Also the potentiated response was eliminated by the combined application of prazosin and alpha,beta-methylene ATP. The non-adrenergic transmitter in the sympathetic nerves of small arteries thus appears to be the dominant transmitter during low-frequency nerve stimulation, causing rapid but phasic activation. Noradrenaline is the most important transmitter for higher frequencies, exerting slower but sustained contractions. The post-stimulatory potentiation affects both the adrenergic and the non-adrenergic part of the neurogenic response.

Vasoconstriction of guinea‐pig submucosal arterioles following sympathetic nerve stimulation is mediated by the release of ATP

“…In a number of vessels where (i-antagonist resistant responses have been recorded, they have been shown to be due to the activation of P2x-purinoceptors by ATP co-released with NA from sympathetic nerves (von Kugelgen & Starke, 1985;Brizzolara & Burnstock, 1990;Sjoblom-Widfeldt et al, 1990). In the present study, arteriolar constrictions were evoked in response to the exogenous application of ATP, mATP and DADPP.…”

“…Hirst & Neild (1980;1981) suggested that the xadrenoceptor resistant responses in this vessel were due to the action of NA through a novel y-adrenoceptor. In a number of other arteries cx-adrenoceptor antagonist resistant contractions following sympathetic nerve stimulation have been recorded (Muramatsu et al, 1989;Sjoblom-Widfeldt et al, 1990;Brizzolara & Burnstock, 1990). These are thought to be due to ATP, which is co-released with NA, acting through P2x-purinoceptors because they are abolished following desensitization of P2x-purinoceptors with the stable adenosine 5'-triphosphate (ATP) analogue cxj-methylene ATP (Ramme et al, 1987;Hirst & Jobling, 1989;Evans & Cunnane, 1992).…”

Purinergic signalling in the gastrointestinal tract and related organs in health and disease

“…Mesenteric arteries supplying the gastrointestinal tract of rat, guinea pig, rabbit and dog have been shown to be innervated by sympathetic nerves in which ATP is a major cotransmitter with NA [78,79,187,357,411,453,493,528,623,689]. For the sympathetic nerves in the jejunal branches of the rabbit mesenteric artery, like those supplying submucosal arterioles, ATP appears to be the sole transmitter, while NA acts prejunctionally [564].…”

Purinergic receptors in the splanchnic circulation

“…Modulation of ATP release by noradrenaline can only be revealed during nerve stimulation of very low frequencies (0.2±2 Hz) and short duration (10 s) [9,117]. Parallel with what has been described on transmitter release, the neurogenic contractions induced by electrical field stimulation of postganglionic sympathetic nerves within splanchnic vessels are biphasic [16,94,144,154]. In dog [115] and rabbit mesenteric arteries [181], the first component is purinergic in nature, develops rapidly, is transient and predominates at low frequencies (1-2 Hz) of stimulation, whereas the second component is adrenergic, develops after the purinergic one, is more long-lasting and becomes more evident as the frequency of stimulation increases (10 Hz).…”