A regional difference in the distribution of postsynaptic alpha-adrenoceptor subtypes in canine veins

1 a-Adrenoceptors present in the vasculature of the nasal mucosa in P-adrenoceptor blocked dogs have been characterized pharmacologically using selective a,-and M2-adrenoceptor agonists and antagonists. 2 In pentobarbitone-anaesthetized dogs, intra-arterial (i.a.) administration of the selective xlagonists cirazoline and phenylephrine, the selective M2-agonist UK-14,304 and the mixed (,/a2-agonists adrenaline, noradrenaline and oxymetazoline produced dose-related nasal vasoconstrictor responses (as measured by decreases in nasal cavity pressure). The rank order of agonist potency was adrenaline > oxymetazoline = UK-14,304 > noradrenaline > cirazoline > phenylephrine.3 The nasal response to cirazoline was inhibited by the selective ml-adrenoceptor antagonist prazosin but not by the new, potent selective M2-adrenoceptor antagonist RX 811059. In contrast, UK-14,304 was inhibited only by RX 811059. Either prazosin or RX 811059 reduced the effect ofthe mixed agonist adrenaline. 4 In spinal dogs, the noradrenaline-evoked fall in nasal cavity pressure was reduced by either prazosin or RX 811059. Prazosin attenuated markedly the nasal vasoconstrictor response to electrical stimulation of postganglionic fibres emerging from the superior cervical ganglion (SNS) whereas RX 811059 was ineffective. Administration of the neuronal re-uptake inhibitor cocaine potentiated the effect of i.a. noradrenaline but reduced marginally the maximal response to SNS. After cocaine, RX 811059 enhanced the effect of SNS and attenuated the response to noradrenaline. Prazosin reduced effectively the responses to both SNS and noradrenaline after cocaine. Pretreatment with the a2-agonist UK-14,304 did not affect the response to noradrenaline in the nasal cavity but evoked a persistent (up to 2 h) reduction in the response to SNS. RX 811059 antagonized the inhibitory effect of UK-14,304. 5These results demonstrate that both postjunctional a,-and a2-adrenoceptors mediating vasoconstriction are present in the canine nasal mucosa. In addition, sympathetic neurones innervating the nasal mucosa are characterized by a very efficient re-uptake process and contain prejunctional a2-adrenoceptors.

Section: Discussionmentioning

confidence: 99%

“…These workers suggested that in the femoral vascular bed there was a predominance of oX2-adrenoceptors whereas in the renal bed a,-adrenoceptors predominate. In addition, Shoji et al (1983) found that the distribution and proportions ofpostjunctional a,-and x2-adrenoceptors varied greatly in fifteen isolated veins taken from dogs.…”

mentioning

confidence: 98%

Characterization of α‐adrenoceptors in the vasculature of the canine nasal mucosa

Berridge

Roach

1986

“…Such an interaction between postjunctional xl-and x2-adrenoceptors may also partially explain the wide disparity in the relative potencies of al-and x2-adrenoceptor antagonists found between vascular preparations (see Drew, 1985;McGrath et al, 1989 (Glusa & Markwardt, 1983;Furuta, 1988), prazosin is only 11-35 fold more potent than yohimbine (De Mey & Vanhoutte, 1981;Shoji et al, 1983). Similarly in the canine isolated splenic artery and vein the rauwolscine and prazosin potency ratio against noradrenaline (both agents produced competitive antagonism) was 12 and 3, respectively (Hieble & Woodward, 1984).…”

Section: The Influence Of Angiotensin IImentioning

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

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.

“…The postjunctional a2-adrenoceptors have been shown to be involved in the mediation of vasoconstriction (Flavahan & McGrath, 1980; Zwieten, 1980;Kobinger & Pichler, 1982;Elliot & Reid, 1983;van Meel et al, 1983) and venoconstriction (Shoji et al, 1983;Steen et al, 1984) responses following sympathetic nerve stimulation or noradrenaline infusion. Recent studies have shown that postjunctional al-adrenoceptors predominate in human mesenteric arteries while postjunctional a2-adrenoceptors predominate in human mesenteric veins (Tmrnebrandt et al, 1985).…”

Section: Introductionmentioning

confidence: 99%

The effects of noradrenaline, B‐HT 920, methoxamine, angiotensin II and vasopressin on mean circulatory filling pressure in conscious rats

Pang

Tabrizchi

1986

1 The effects of vasoactive substances on mean circulatory filling pressure (MCFP), an index of total body venous tone, were determined in conscious rats.2 Cumulative doses of saline (0.9% w/v NaCl solution), methoxamine (xl-adrenoceptor agonist), B-HT 920 (a2-adrenoceptor agonist) noradrenaline and vasopressin, and individual doses of angiotensin II (AII), were infused into the rats. Mean arterial pressure (MAP), MCFP and heart rate (HR) were determined before and during the plateau responses to infusions of the vasoactive substances. 3 The infusions of all the agonists caused a dose-dependent increase in MAP and a decrease in HR. The infusion of saline affected neither MAP nor HR. 4 The infusions of saline and methoxamine did not affect MCFP while the infusions of B-HT 920, noradrenaline and AII increased MCFP. MCFP was slightly increased during the infusion of high doses of vasopressin. 5 It was concluded that receptors for the X2-adrenoceptor agonist and AII are involved in the control of venous tone. Receptors for the a,-adrenoceptor agonist and vasopressin are not important for the control of venous tone.