Evidence for prazosin‐resistant, rauwolscine‐sensitive α‐adrenoceptors mediating contractions in the isolated vascular bed of the rat tail

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1The effects of nitric oxide (10-6 M), NW-nitro-L-arginine methylester (L-NAME, 10-M, an inhibitor of nitric oxide synthase), endothelium removal, hypoxia and selective ax-adrenoceptor antagonists on responses to nerve electrical field-stimulation (EFS) were studied in the rabbit isolated pulmonary artery.2 EFS induced frequency-dependent contractions which were abolished by prazosin (xi-adrenoceptor antagonist) and unaffected by rauwolscine (M2-adrenoceptor antagonist). EFS-induced responses were potentiated by L-NAME and inhibited by nitric oxide. The effect of L-NAME was reversed by the presence of L-arginine (2 x 10-4 M), which had no effect on its own. In the presence of L-NAME, the EFS-induced responses were reduced by rauwolscine and the residual responses were abolished by prazosin. 3 Removal of the vascular endothelium increased the maximum contractile response to EFS but did not inhibit the ability of L-NAME to potentiate contractile responses to EFS. 4 Hypoxia inhibited the contractile response to EFS. This effect of hypoxia was also seen in the presence of L-NAME and in endothelium rubbed preparations. 5 In conclusion, the endothelium modulates EFS-induced contractions in the rabbit pulmonary artery. The contraction induced by EFS was inhibited by nitric oxide, but potentiated by the nitric oxidesynthase inhibitor, L-NAME. The effect of L-NAME was not mediated solely through the endothelium and revealed involvement of a2-adrenoceptors in EFS-induced contraction. Hypoxia inhibited neurogenic responses in rabbit isolated pulmonary arteries.

Section: Discussionmentioning

confidence: 99%

Influences of the endothelium and hypoxia on neurogenic transmission in the isolated pulmonary artery of the rabbit

MacLean

McCulloch

Macmillan

et al. 1993

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“…For example it has been reported that the expression of postjunctional CX2-adrenoceptor-mediated responses to UK-14304 in the rabbit distal saphenous artery is dependent upon the presence of angiotensin II (All) (Dunn et al, 1989). Similarly, in the perfused isolated tail of the rat a2-adrenoceptor-mediated responses are observed only after raising tone with, for example vasopressin or endothelin (Templeton et al, 1989;MacLean & McGrath, 1990), while in the canine saphenous artery a non-contractile concentration of Bay K 8644 allowed the demonstration of responses mediated by the subtype (Sulpizio & Hieble, 1987).…”

Section: Introductionmentioning

confidence: 99%

Postjunctional α‐adrenoceptors in the rabbit isolated distal saphenous artery: indirect sensitivity to prazosin of responses to noradrenaline mediated via postjunctional α₂‐adrenoceptors

Dunn

McGrath

Wilson

1991

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1Under normal experimental conditions, the rabbit isolated distal saphenous artery appears to contain a homogeneous population of postjunctional ae-adrenoceptors. Prazosin 4 The responses to NA, after the protection protocol, in the presence of All, were susceptible to the selective a2-adrenoceptor antagonist, rauwolscine (1 M), but resistant to the selective a,-adrenoceptor antagonist prazosin (0.1 pM). Furthermore, the combination of rauwolscine (1 M) and prazosin (0.1 IpM) was no more effective in blocking responses to NA than was rauwolscine (1 pM) alone. These results are consistent with the presence of a homogeneous population of postjunctional oc2-adrenoceptors. 5 Inducing a small degree of tone with a low concentration of the selective ac-adrenoceptor agonist, phenylephrine, markedly increased the threshold sensitivity to the selective a2-adrenoceptor agonist UK-14304, in a manner analogous to that seen with All. 6 The results in the present study indicate that responses mediated via postjunctional a2-adrenoceptors in the rabbit isolated distal saphenous artery are dependent upon a degree of vascular smooth muscle stimulation by some other receptor system. It is hypothesized that under normal experimental conditions, this function is fulfilled by stimulation of al-adrenoceptors, while after ax-adrenoceptor blockade the necessary positive influence can be provided by stimulation of All receptors. The implications for such an interaction between postjunctional a-adrenoceptor subtypes in demonstrating prazosin-resistant, rauwolscine-or yohimbine-sensitive responses in isolated blood vessels is discussed.

“…Thus, even though no functional response was observed in this vessel, M2-adrenoceptor binding sites were detected and they appear to be located almost exclusively on the smooth muscle. We are currently examining the possibility that a2-adrenoceptor-mediated contraction in the splenic artery can be uncovered by the presence of an ancillary spasmogen, as previously described in the rat isolated tail artery (Templeton et al, 1989) and rabbit isolated distal saphenous artery (Dunn et al, 1991).…”

Section: Saturation Studies In Other Porcine Blood Vesselsmentioning

confidence: 99%

“…The KrebsHenseleit saline was maintained at 31 C for the ear vein, and at 37TC for the SA and TA, and gassed with 95%02/5%CO2. The superficial blood vessels were maintained at 31 C because previous studies have shown that M2-adrenoceptor function is enhanced at lower temperature (Flavahan & Vanhoutte, 1986;Templeton et al, 1989). No attempt was made to remove the endothelium.…”

Section: Functional Studiesmentioning

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

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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...