Neurotransmission in Human Resistance Arteries: Contribution of &amp;alpha;&lt;sub&gt;1&lt;/sub&gt;- and &amp;alpha;&lt;sub&gt;2&lt;/sub&gt;- Adrenoceptors but Not P&lt;sub&gt;2&lt;/sub&gt;- Purinoceptors

Stephens, N. L.; Sj, Bund; Eb, Faragher; Heagerty, AM

doi:10.1159/000158950

Cited by 14 publications

(16 citation statements)

References 10 publications

(13 reference statements)

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“…Therefore, it is not possible at this stage to draw a conclusion about which receptor subtypes mediate NA-induced constrictions of distal arterioles and proximal cutaneous arteries in the guinea-pig ear. However, the relative potencies of yohimbine and prazosin found in the present study, are consistent with findings in proximal versus distal arteries in other cutaneous vascular beds, both in laboratory animals (Medgett & Ruffolo, 1988) and in man (Flavahan et al, 1987;Nielsen et al, 1989;Parkinson et al, 1992;Stephens et al, 1992). Furthermore, a preferential distribution of al-adrenoceptors in proximal arteries and a2-adrenoceptors in distal arterioles has been found in skeletal muscle vascular beds (Faber, 1988;Ohyanagi et al, 1991).…”

Section: Discussionsupporting

confidence: 92%

Blockade of noradrenaline‐induced constrictions by yohimbine and prazosin differs between consecutive segments of cutaneous arteries in guinea‐pig ears

Morris¹

1994

British J Pharmacology

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1 The study has examined the receptors mediating constriction produced by brief local application of noradrenaline (NA) to cutaneous arteries and arterioles in the ear vasculature of anaesthetized guineapigs. The innervation of the corresponding vascular segments has been examined immunohistochemically at the conclusion of the pharmacological experiments. 2 Small arteries of branch order 4 (4°, Jim internal diameter) were more sensitive to the vasoconstrictor action of NA than were more proximal arteries of branch order 3 (3°, 60-150 pim internal diameter), or more distal arteries and arterioles of branch orders 5 to 7 (5°-70, 18-85 fim internal diameter). This higher sensitivity of 4°arteries was maintained after blockade of neuronal uptake with desipramine (1 JAM), and after blockade of P-adrenoceptors with propranolol (1 jiM).3 NA-induced vasoconstrictions of distal arterioles (5°-7°) were abolished or greatly reduced by yohimbine (1 JM). The blockade by yohimbine decreased progressively with increasing vessel diameter of proximal arteries, while the blockade by prazosin (1I JM) increased progressively in arteries >40 gLm diameter. 4 In 3°and 4°arteries, a substantial component (approximately 50%) of NA-induced vasoconstrictions remained after combined treatment with yohimbine and prazosin, in the presence or absence of desipramine. These constrictions were not further reduced by benextramine (1-10 JM), but were abolished by dihydroergotamine (1-10 IAM). Constrictions induced by ATP (0.1-1 mM) were not affected by dihydroergotamine. 5 5-Hydroxytryptamine (3-100 JAM) had a variable effect on 3°and 4°arteries including: concentrationdependent constrictions (n = 3); small constrictions at some concentrations, and dilatations or no change in diameter at other concentrations (n = 6); concentration-dependent dilatations only (n = 3). The 5-HT2 receptor antagonist, ketanserin (0.1-0.31M), did not affect NA-induced constrictions. 6 In 16 arterial segments ranging from 3°arteries to 60 arterioles, there was a significant correlation between the presence of neuropeptide Y-immunoreactive (NPY-IR) sympathetic axons and the degree of blockade of NA-induced constrictions by yohimbine, prazosin and dihydroergotamine. 7 These results demonstrate marked differences in the postsynaptic adrenoceptors mediating vasoconstriction to a bolus of NA applied briefly to the adventitial surface of different segments of the cutaneous vasculature of the guinea-pig ear. Furthermore, the presence or absence of adrenoceptors sensitive to blockade by yohimbine or prazosin is related to the proportion of sympathetic axons innervating each vascular segment which contain NPY-IR.

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Section: Discussionsupporting

confidence: 92%

Blockade of noradrenaline‐induced constrictions by yohimbine and prazosin differs between consecutive segments of cutaneous arteries in guinea‐pig ears

Morris¹

1994

British J Pharmacology

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“…This is consistent with previous results performed in the human gastroepiploic artery, using another a 2 -adrenoceptor antagonist, yohimbine (Toda et al, 1988). Our results support the hypothesis that the predominant effect of a 2 -adrenoceptors in human blood vessels may be postjunctional (Toda et al, 1988;Parkinson et al, 1992;Stephens et al, 1992).…”

Section: Fukui Et Al Neurotransmission In Human Arterysupporting

confidence: 90%

“…However, purinergic transmission cannot be confirmed in human arterial blood vessels (Parkinson et al, 1992;Stephens et al, 1992), although sympathetic vasomotor …”

Section: Discussionmentioning

confidence: 99%

“…Later results from investigations on human isolated resistance arteries disputed this hypothesis, indicating that both a 1 -and a 2 -adrenoceptors are activated postjunctionally by neurally released NA (Stevens & Moulds, 1985;Parkinson et al, 1992;Stephens et al, 1992). Recently, we observed that both a 1 -and a 2 -adrenoceptors contributed to the vasoconstrictor responses to exogenously applied NA in human isolated, perfused gastroepiploic arteries (Fukui & Chiba, 2003).…”

Section: Introductionmentioning

confidence: 95%

“…However, the functional evidence obtained in in vitro human arterial tissues suggest that neurally evoked vasoconstriction contains an adrenergic component, but has no purinergic component (Parkinson et al, 1992;Stephens et al, 1992). In the human saphenous vein, the presence of a purinergic component for mediating sympathetic vasomotor responses has been described (Rump & von Ku¨gelgen, 1994;Racchi et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

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

Fukui

Yang

Chiba

2005

British J Pharmacology

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1 The contribution of postjunctional P2X receptors and subtypes of a-adrenoceptors to vasoconstrictor responses following periarterial electrical nerve stimulation (PNS, 30 s trains of pulses at a frequency of 2, 4 or 8 Hz) was investigated in human gastroepiploic arteries. 2 The vasoconstrictor response to PNS at a stimulation of 4 or 8 Hz was a two-peaked response, whereas at a frequency of 2 Hz it appeared only as a late peak. All vasoconstrictions evoked by PNS were abolished by phentolamine, a nonselective a-adrenoceptor inhibitor, but not by a,b-methylene ATP, a P2X receptor-desensitizing agent. 3 The early peak to PNS at 4 or 8 Hz was abolished by prazosin, an a 1 -adrenoceptor antagonist, while the late one still remained, although it was markedly inhibited. The responses remaining after prazosin were blocked by rauwolscine. The vasoconstrictor response to PNS at 2 Hz was not affected by prazosin (0.1 mM), but was abolished by rauwolscine (0.1 mM), an a 2 -adrenoceptor antagonist. 4 OPC-28326(10 mM), a newly developed vasodilator, which preferentially exerts its antagonistic actions on the a 2B -and a 2C -adrenoceptors, significantly reduced the noradrenaline-induced vasoconstriction in the absence or presence of prazosin. OPC-28326 had a greater inhibitory effect on the late peak evoked by PNS than the early one. The neurogenic responses remaining after OPC-28326 were abolished by prazosin. 5 The present results suggest that sympathetic vasoconstriction of the human gastroepiploic artery is mediated by both a 1 -and a 2 -adrenoceptors postjunctionally, but not by P2X receptors. The a 2 -adrenoceptors may be preferentially activated at a low frequency of stimulation, which induces a constriction more slowly than that by a 1 -adrenoceptors. The existence of a 2 -adrenoceptors may cause an enhancement of a 1 -adrenoceptor-induced responses.

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P2X receptors in the cardiovascular system

Ralevic

2012

WIREs Membr Transp Signal

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P2X receptors are ligand‐gated ion channels activated by ATP. They are trimeric receptors formed from P2X subunit proteins (P2X1–7), which can associate as homomers or heteromers. Among the P2X receptors, the P2X1 receptor is most widely distributed in the cardiovascular system, being expressed on the smooth muscle of most blood vessels investigated. It mediates contraction to ATP coreleased with noradrenaline as a sympathetic neurotransmitter. P2X receptors are also expressed in the heart and mediate an increase in myocyte contractility, an effect in which the P2X4 receptor is important. Prejunctional P2X3 and P2X2/3 receptors on cardiac sympathetic neurones may, through positive feedback, amplify sympathetic neurotransmission. More recently, P2X receptors have been discovered on endothelial cells with immunoreactivity for P2X1–7 receptor proteins variously having been shown, and a role identified for the P2X4 receptor as a mediator of endothelium‐dependent vasodilatation during shear stress. Their widespread expression in the heart and vasculature identifies P2X receptors as potential targets for the development of drugs to treat cardiovascular disease. WIREs Membr Transp Signal 2012, 1:663–674. doi: 10.1002/wmts.58 For further resources related to this article, please visit the http://wires.wiley.com/remdoi.cgi?doi=10.1002/wmts.58.

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Neurotransmission in Human Resistance Arteries: Contribution of α<sub>1</sub>- and α<sub>2</sub>- Adrenoceptors but Not P<sub>2</sub>- Purinoceptors

Cited by 14 publications

References 10 publications

Blockade of noradrenaline‐induced constrictions by yohimbine and prazosin differs between consecutive segments of cutaneous arteries in guinea‐pig ears

Blockade of noradrenaline‐induced constrictions by yohimbine and prazosin differs between consecutive segments of cutaneous arteries in guinea‐pig ears

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

P2X receptors in the cardiovascular system

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Neurotransmission in Human Resistance Arteries: Contribution of &alpha;<sub>1</sub>- and &alpha;<sub>2</sub>- Adrenoceptors but Not P<sub>2</sub>- Purinoceptors

Cited by 14 publications

References 10 publications

Blockade of noradrenaline‐induced constrictions by yohimbine and prazosin differs between consecutive segments of cutaneous arteries in guinea‐pig ears

Blockade of noradrenaline‐induced constrictions by yohimbine and prazosin differs between consecutive segments of cutaneous arteries in guinea‐pig ears

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

P2X receptors in the cardiovascular system

Contact Info

Product

Resources

About

Neurotransmission in Human Resistance Arteries: Contribution of α<sub>1</sub>- and α<sub>2</sub>- Adrenoceptors but Not P<sub>2</sub>- Purinoceptors

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