Heterogeneity of Postjunctional α-Adrenoceptors in Isolated Mesenteric Resistance Arteries from Rats, Rabbits, Pigs, and Humans

Nielsen, Henning Κ.; Hk, Pilegaard; Jm, Hasenkam; Mortensen, Frank Viborg; Mj, Mulvany

doi:10.1097/00005344-199107000-00002

Cited by 19 publications

(18 citation statements)

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“…It is therefore possible, that the selectivity of B-HT 933 could be compromised with the high concentrations used, and the observed contraction may be due to nonspecific stimulation of a1 -receptors. For comparison, Nielsen et al [31,32] found pD2 values of 5.19 and 6.1 1 in human mesenteric and human subcutaneous arteries, respectively.…”

Section: Advmoceptovsmentioning

confidence: 99%

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Adrenergic responses in human small arteries isolated from the femoral neck

Lundgaard

Aalkjær

Bünger

et al. 2001

Journal Orthopaedic Research

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Many pathological bone conditions are accompanied by changes in bone perfusion. However, no method has yet allowed investigation of vascular reactivity in human bone tissue. In the present study, arterial segments (diameter = 0.25 mm) were isolated from human bone biopsies and mounted as ring preparations in vitro. The viability of the arteries and the effects of adrenoceptor stimulations were investigated. Combined a-and 0-adrenoceptor stimulation (noradrenaline 10-8-10-5 M) and specific cyIadrenoceptor stimulation (phenylephrine, 10-8-10-4.5 M ) induced ' concentration-dependent contractions in all arteries. Selective stimulation of a2-receptors (B-HT 933, 1 O-R-10-'.5 M) only induced contraction in three of eight arteries. Stimulation of 0-receptors with isoprenaline ( M ) resulted in vasorelaxation in 3 of 10 arteries. In all arteries, acetylcholine ( 10-'0-10-5 M ) induced vasorelaxation, demonstrating preserved function of the endothelium. The results suggest that primarily a1 -receptors are responsible for adrenoceptor induced vasoconstriction in human bone while functional a?-and 0-receptors may not be consistently expressed. The model is the first to allow investigations on vascular reactivity in human bone tissue and may become valuable for assessment of both normal and pathological bone physiology.

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Section: Advmoceptovsmentioning

confidence: 99%

“…Adrenoceptors show great variability between species and between different vascular beds within the same species [23,32]. In the perfused tibia in dogs, both 31-and cl2-receptors have been demonstrated.…”

Section: Advmoceptovsmentioning

confidence: 99%

Adrenergic responses in human small arteries isolated from the femoral neck

Lundgaard

Aalkjær

Bünger

et al. 2001

Journal Orthopaedic Research

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“…While in small mammals, vasoconstriction of small arteries appears to be mediated exclusively by activation of α 1 -adrenoceptors (Angus et al 1988;McGrath et al 1989), in porcine and human blood vessels α 2 -adrenoceptors have been found to contribute to the overall contractile activity of noradrenaline (NA) (Nielsen et al 1991). Recently Wright et al (1995) have reported that different porcine isolated blood vessels, including the splenic artery (SA), have different expression of functional α 2 -adrenoceptors.…”

Section: Introductionmentioning

confidence: 99%

Pharmacological characterization of α-adrenoceptors that mediate contraction in splenic artery strips from the pig

Barbieri

Santagostino-Barbone

Zonta

et al. 1998

Naunyn-Schmiedeberg's Arch Pharmacol

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The alpha-adrenoceptors that mediate contractions in strips of splenic artery from the pig were characterized by the use of selective agonists and subtype-selective antagonists. Noradrenaline, the alpha1-selective agonist phenylephrine and the alpha1-/alpha2-agonist oxymetazoline caused the preparations to contract with potency (pD2) values of 6.94, 6.14 and 7.27, respectively. Compared to noradrenaline, phenylephrine and oxymetazoline induced 93% and 78% of noradrenaline maximum effect. Conversely, the two alpha2-selective agonists clonidine and B-HT 920 induced only 31% and 13% of noradrenaline maximum effect. B-HT 920 only marginally contracted the tissue even when it was precontracted with phenylephrine. The alpha2-selective antagonist yohimbine antagonized oxymetazoline- and phenyleprine-induced contractions with affinity (pA2) values (6.80 and 6.74, respectively) consistent with alpha1-adrenoceptor interaction. This suggests that the pig splenic artery possesses only functional alpha1-adrenoceptors. The alpha1-adrenoceptor antagonists of varying subtype selectivities like WB-4101, 5-methylurapidil, benoxathian and BMY 7378 competitively antagonized phenylephrine-induced contractions with affinity values of 9.46, 8.26, 9.06 and 6.91, respectively. These values correlated highly with published affinity values for functional alpha1A-adrenoceptors (r=0.92) and alpha1a-clones (r=0.94) and less well with affinity values for functional alpha1B-adrenoceptors (r=0.84) and alpha1b-clones (r=0.87). Conversely, correlation with functional alpha1D-adrenoceptors (r=0.26) and alpha1d-clones (r=0.33) was poor. In addition the alpha1D-selective antagonist BMY 7378 had a low affinity value compared to that reported for alpha1D-adrenoceptors. Therefore, based on correlation studies, the plot that resembled the line of equal values most closely was that for the alpha1A-subtype. The alpha1A-selective antagonist RS-17053 antagonized phenylephrine-induced contractions in an apparently non-competitive manner and gave an apparent pA2 value of 7.06 which is similar to the "low" affinity values reported in other alpha1A-containing tissues. Exposure to the irreversible alpha1B/D-antagonist chloroethylclonidine slightly decreased maximum response to phenylephrine without significantly affecting its potency value, indicating that the phenylephrine response is substantially chloroethylclonidine-insensitive. It is concluded that splenic artery strips from the pig contract in response to phenylephrine through activation of alpha1-adrenoceptors which display the pharmacological profile of the alpha1A-subtype for which the recently reported alpha1A-selective antagonist RS-17053 shows low affinity. Evidence for contribution of the alpha1B-subtype in the overall contractile response is elusive while no evidence was obtained for the involvement of the alpha1D-subtype. The contribution of functional alpha2-adrenoceptors to the contractile response was ruled out.

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“…However, overt a2-adrenoceptor mediated contractions have been observed in a range of non-conduit/distal arteries and veins not generally used for routine experimentation, such as human arterioles (Nielsen et al, 1989), canine saphenous vein (Flavahan & Vanhoutte, 1986), rabbit saphenous vein (Daly et al, 1988), and feline middle cerebral artery (Fredholm et al, 1985). 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).…”

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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Heterogeneity of Postjunctional α-Adrenoceptors in Isolated Mesenteric Resistance Arteries from Rats, Rabbits, Pigs, and Humans

Cited by 19 publications

References 0 publications

Adrenergic responses in human small arteries isolated from the femoral neck

Adrenergic responses in human small arteries isolated from the femoral neck

Pharmacological characterization of α-adrenoceptors that mediate contraction in splenic artery strips from the pig

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

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