Heterogeneity of neurogenic responses in intra‐ and extrameningeal arteries of dogs

Abstract

1 Neurogenic responses to transmural electrical stimulation were examined in endothelium-denuded extrameningeal (vertebral and carotid) and intrameningeal (spinal, basilar and middle cerebral) arteries isolated from dogs. 2 In the extrameningeal arteries, transmural electrical stimulation produced a phasic contraction. This contraction was abolished by tetrodotoxin, prazosin and guanethidine. However, a,fi-methylene ATP and N0-nitro-L-arginine (L-NOARG) had no significant effect on the contractile responses. 3 In the intrameningeal arteries, the neurogenic responses to electrical stimulation were composed of a transient contraction and relaxation. The transient contraction was selectively inhibited by guanethidine or after desensitization of P2x-purinoceptors with a,fi-methylene ATP. L-NOARG abolished the relaxation but not the contraction induced by electrical stimulation. Prazosin had no effect on either neurogenic response. 4 Noradrenaline produced a large contraction in the extrameningeal arteries which was selectively inhibited by prazosin. a,fl-Methylene ATP produced neither contraction nor inhibition of the response to noradrenaline in the extrameningeal arteries.5 In the intrameningeal arteries, a,fl-methylene ATP produced a greater contraction than noradrenaline. The response to a,#-methylene ATP was selectively abolished by desensitization of P2X-purinoceptors with a,f,-methylene ATP itself. The contractile response to noradrenaline was inhibited by rauwolscine but not by prazosin. 6 ATP produced endothelium-dependent relaxations in the extrameningeal and intrameningeal arteries, which were attenuated by endothelium removal. 7 NADPH diaphorase-positive fibres were dense in the middle cerebral and basilar arteries but rare or absent in the spinal artery. In the extrameningeal arteries diaphorase-positive traces were observed in the vasa vasorum.8 The present findings indicate that the neurogenic responses of intrameningeal arteries of dogs are composed of NO-ergic and sympathetic purinergic components, while the extrameningeal arteries tested produced only sympathetic adrenergic responses, suggesting that regional heterogeneity may be associated with a sudden transition in innervation and receptor expression at the meninx.

Evidence that tachykinins are the main NANC excitatory neurotransmitters in the guinea‐pig common bile duct

“…There is ample evidence that guanethidine, besides preventing noradrenaline release in pretreated tissues, also blocks ‘purinergic’ responses to sympathetic nerve stimulation (see e.g. Kohno et al , 1995; Morris, 1994) as well as ATP release from sympathetic neurons (Todorov et al , 1996) in a concentration range (up to 10 μM) close to that used in our study (3 μM). Likewise, the present experiments with guanethidine provide evidence that neuropeptide Y, stored in sympathetic nerves, is not involved in the EFS‐induced response, since also the release of this transmitter is prevented by guanethidine (see e.g.…”

ATP-Evoked Sustained Vasoconstrictions Mediated by Heteromeric P2X1/4 Receptors in Cerebral Arteries

“…Together with literature evidence allow us to hypothesize that only P2X1 and P2X4 subunits compose the functional P2XR structures in major mammalian arteries. Moreover, our preliminary results 40 in rat cerebral arteries suggest the predominance of the purinergic simulation in the rat cerebral vasculature over adrenergic which is in accordance with the data obtained in dog 41 and human 42 cerebral arteries. Additional focused studies will be needed to establish the role of individual subtypes in pathological conditions.…”

The birth and postnatal development of purinergic signalling

“…,Kohno et al (1995),Pacaud et al (1995),Malam-Souley et al (1996),Miyagi et al (1996),Orre et al (1996),Harper et al (1998),Muraki et al (1998), Abebe & Mustafa(2002),Fiser et al (2002),Nayeem & Mustafa (2002),Yaar et al (2002) …”