Neuronally released norepinephrine does not preferentially activate postjunctional alpha 1-adrenoceptors in human blood vessels in vitro.

Stevens, M. J.; Moulds, R. F. W.

doi:10.1161/01.res.57.3.399

Cited by 23 publications

(11 citation statements)

References 19 publications

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“…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: 94%

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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Section: Introductionmentioning

confidence: 94%

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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“…The neurogenic vasoconstrictor response to LBNP is influenced by both the amount ofNE released from sympathetic nerves (facilitated by prejunctional beta receptor stimulation) and by the vascular responsiveness to neurally released NE. Both the neurally released and the exogenous NE stimulate postjunctional alpha-l and alpha-2 vascular adrenoceptors equally (24,25). The vascular responses to the neurally released NE could have been altered during the course of these experiments by postjunctional effects of isoproterenol and epinephrine and by changes in resting FVR.…”

Section: (I) Experimental Designmentioning

confidence: 99%

Epinephrine facilitates neurogenic vasoconstriction in humans.

Floras¹,

Aylward²,

Victor³

et al. 1988

J. Clin. Invest.

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Numerous studies have suggested that epinephrine may facilitate neural release of NE. There have been no studies in humans that demonstrate the functional significance of this action. To determine whether epinephrine facilitates neurogenic vasoconstriction in humans, we contrasted forearm vasoconstrictor responses to a reflex stimulus (lower body negative pressure ILBNPI) and to intraarterial NE before, during, and 30 min after infusion of epinephrine (50 ng/min) or isoproterenol (10 or 25 ng/min) into a brachial artery. These doses had no systemic effects. We reasoned that if prejunctional stimulation of beta receptors by epinephrine and isoproterenol had functional significance, the vasoconstrictor response to LBNP would be potentiated in comparison to the response to NE (postjunctional mechanism).Studies were done on 23 normal male volunteers. Forearm blood flow was measured with a strain gauge plethysmograph and intraarterial pressure was recorded. The ratio of vasoconstrictor responses to LBNP/NE was used as an index of neural release of the neurotransmitter NE. This ratio increased during infusions of both epinephrine and isoproterenol. 30 min after epinephrine the vasoconstrictor response to LBNP (n = 15) was augmented from +9.9±2.2 (SE) resistance units (RU) before epinephrine to +16.4±3.2 RU (P < 0.05); whereas the response to NE (n = 8) tended to decrease from +8.8±3.1 RU before to +4.2±1.2 RU after epinephrine (P > 0.05). In contrast, 30 min after isoproterenol the vasoconstrictor responses to LBNP and NE were the same as before isoproterenol. The augmented ratio of responses to LBNP/NE after epinephrine and not after isoproterenol supports the concept that epinephrine, but not isoproterenol, is taken up by the adrenergic terminal, is released subsequently during reflex stimulation, and augments the release of the neurotransmitter NE.These experiments provide the first hemodynamic evidence in humans that epinephrine and isoproterenol facilitate neurogenic vasoconstriction. The sustained effect of epinephrine in contrast to isoproterenol suggests that the late facilitation Parts of this work were presented at

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“…A comparative study by Nielsen et al (1991) examined the pharmacological characteristics of x-adrenoceptor-mediated contractions to noradrenaline in similar sized mesenteric arteries (200 fym diameter) from the rat, rabbit, pig and man and found a2-adrenoceptor-mediated contractions detectable only in porcine and human blood vessels. Further, there are reports that indicate that ml-and a2-adrenoceptors participate in sympathetically mediated vasoconstriction of human vessels (Stevens & Moulds, 1985;Parkinson et al, 1992), yet a-adrenoceptor mediated constrictor responses in small arteries from the rat, guinea-pig and rabbit appear to be exclusively via al-adrenoceptors (Angus et al, 1988;McGrath et al, 1989). It seems likely that in small mammals, neuronally activated x2-adrenoceptors reside on blood vessels too small for routine experimentation (see Ohyanagi et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

The relationship between density of α‐adrenoceptor binding sites and contractile responses in several porcine isolated blood vessels

Wright

Blaylock

Kendall

et al. 1995

British J Pharmacology

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1 The aim of this study was to investigate constrictor x-adrenoceptors in three isolated blood vessles of the pig, the thoracic aorta (TA), the splenic artery (SA) and marginal ear vein (MEV) and then compare the functional response with the densities of a,-and M2-adrenoceptor binding sites in these and several other porcine vascular tissues, palmar common digital artery (PCDA), palmar lateral vein (PLV) and ear artery (EA).2 Noradrenaline (NA), phenylephrine (PE) and UK14304 (all at 0.03-10gM) elicited concentrationdependent contractions in the TA and MEV, with a rank order of potency of UK14304>NA>PE. UK14304 produced maximal responses which were 58% (TA) and 65% (MEV) of that of NA. In the SA, UK14304 and PE produced maximal responses which were less than 10% and 50% of the NA-induced maximal response respectively, with an order of potency of NA>PE. In the SA, NAinduced contractions were competitively antagonized by prazosin (pA2 = 8.60 ± 0.15). Further, rauwolscine (1-1O M) antagonized NA-induced contractions with an apparent pKB of 6.09 ± 0.11 (n = 6), indicating an action at al-adrenoceptors. The combination of the two antagonists at concentrations selective for al-(0.1 JLM) and a2-adrenoceptors (1 J4M) had no greater effect than either antagonist alone.This suggests that the SA expresses only post-junctional a1-adrenoceptors.3 In the TA, prazosin produced non-parallel shifts in the NA-induced CRC and this was also observed with rauwolscine, where reductions in the maximal responses were also observed. In the MEV, prazosin was largely inactive in antagonizing NA-induced contractions. In both these vessels a combination of these two antagonists had a greater effect than either alone, indicating the presence of functional a,-and M2-adrenoceptors. The post-junctional x2-adrenoceptors in all of these vessels were resistant to prazosin, suggesting the a2-adrenoceptor to be of the a2A/2D subtype. mg-', n = 4), followed by the PCDA (256.7 ± 22.7 fmol mg', n = 4), the PLV and SA having approximately equal density (143.6 ± 3.9 and 159.1 ± 7.0 fmol mg-' respectively, n = 4 for both), followed by the EA (91.3 ± 10.5 fmol mg-', n = 3) and the MEV had the lowest density (48.9 ± 11.4 fmol mg-', n = 3).7 In saturation studies using [3H]-RX821002, all tissues produced single site saturation curves with no differences in the Kd values (range 1.31 ± 2.16 nM) but the highest densities were found in the TA and MEV (545.3 ± 36.2 and 531.0 ± 40.9 fmol mg-' respectively), followed by the PLV (418.4 ± 39.4 fmol mg-'), then the EA (266.3 ± 40.0 fmol mg-'), and low densities of [3H]-RX821002 binding being found in the PCDA and SA (155.9 ± 18.1 and 117.5 ± 19.3 fmol mg-' respectively). 8 The pattern of binding site distribution for ol-and C2-adrenoceptors is in reasonable agreement with functional studies carried out in these porcine vascular tissues; the TA has the highest densities of a,-and X2-adrenoceptors; in the SA and PCDA there is a predominance (although small) of al-adrenoceptor binding sites, the reverse of which is obse...

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Neuronally released norepinephrine does not preferentially activate postjunctional alpha 1-adrenoceptors in human blood vessels in vitro.

Cited by 23 publications

References 19 publications

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

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

Epinephrine facilitates neurogenic vasoconstriction in humans.

The relationship between density of α‐adrenoceptor binding sites and contractile responses in several porcine isolated blood vessels

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Neuronally released norepinephrine does not preferentially activate postjunctional alpha 1-adrenoceptors in human blood vessels in vitro.

Cited by 23 publications

References 19 publications

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

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

Epinephrine facilitates neurogenic vasoconstriction in humans.

The relationship between density of α‐adrenoceptor binding sites and contractile responses in several porcine isolated blood vessels

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

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