Postsynaptic α1- and α2-adrenoceptor involvement in the vascular responses to neuronally released and exogenous noradrenaline in the hindlimb of the dog and cat

Gardiner, Jennifer C.; Peters, Christopher J.

doi:10.1016/0014-2999(82)90201-1

Cited by 47 publications

(16 citation statements)

References 17 publications

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“…Prazosin at the highest dose applied (1.2 mg/kg, Group B) did not completely abolish the flow reductions during nerve stimulation ( Figure 3), but these prazosin-resistant flow reductions were further attenuated by 0.3 mg/kg rauwolscine. Similar additive effects of a r and a 2 -blockade on stimulationinduced pressure increases have been demonstrated in the canine femoral bed 12 and in pithed rats and rabbits. 20 These data suggest a contribution of vascular a 2 -adrenergic receptors to sympathetic vasoconstriction both under conditions of constant flow as well as of activated metablic counterregulation.…”

Section: Discussionsupporting

confidence: 72%

Sympathetic vasoconstriction sensitive to alpha 2-adrenergic receptor blockade. No evidence for preferential innervation of alpha 1-adrenergic receptors in the canine femoral bed.

Elsner¹,

Saeed²,

Sommer³

et al. 1984

Hypertension

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SUMMARY In the canine femoral bed, we studied the involvement of vascular o 2 -adrenergic receptors in vasoconstriction by stimulating the sympathetic nerve during different degrees of activation of metabolic counter-regulation (constant pressure and constant flow perfusion). In chloraloseanesthetized, despinalized dogs under /3-blockade (2 mg/kg nadolol) and under a constant femoral perfusion pressure, cumulative doses of rauwolscine (0.03, 0.3, and 3.0 mg/kg i.v., n = 8) or of prazosin (0.012, 0.12, and 1.2 mg/kg i.v., n = 8) caused dose-dependent shifts to the right of the doseresponse curve of intraarterial norepinephrine (NE) infusions. These cumulative doses also caused attenuations of the vasoconstriction initiated by lumbar sympathetic stimulation (0.1, 0.3, 1.0, and 3.0 Hz). Sham treatment (n = 8) had no such results. In experiments with constant flow perfusion (n = 6 for each antagonist), rauwolscine shifted the NE dose-response curve significantly more compared to the experiments with constant pressure perfusion, while prazosin was similarly effective under both conditions. Under constant flow perfusion, both antagonists dose-dependently attenuated the vasoconstrictions caused by sympathetic stimulation. While prazosin and sham treatment did not modify the overflow of NE from the femoral bed during stimulation, this overflow was augmented by rauwolscine during stimulation at 3 Hz, which indicated presynaptic modulation of NE release. Under both experimental conditions, no significant difference could be observed in the attenuation of lowfrequency sympathetic vasoconstriction by the two antagonists, when dosages were compared on the basis of their action against infused NE. It is concluded that both a rauwolscine-sensitive component and a prazosin-sensitive component are involved in the competition between sympathetic vasoconstriction and metabolic dilation. The vascular a-adrenergic receptors activated by these two components have a similar postsynaptic localization relative to the nerve endings. (Hypertension 6: 915-925, 1984) KEY WORDS • prazosin • rauwolscine • constant flow perfusion • constant pressure perfusion • intrasynaptic a-adrenergic receptors T HERE is general agreement that more than one type of postsynaptic vascular a-adrenergic receptor exists in laboratory mammalian species'-2 and in humans. 3 " 3 Norepinephrine (NE) induces vasoconstriction by activation of both a,-and a 2 -adrenergic receptors, which have been classified according to the effects of selective pharmacological agonists and antagonists.6 Recently, it has been shown that a 2 -meFrom the Institut fur Angewandte Physiologie

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Section: Discussionsupporting

confidence: 72%

Sympathetic vasoconstriction sensitive to alpha 2-adrenergic receptor blockade. No evidence for preferential innervation of alpha 1-adrenergic receptors in the canine femoral bed.

Elsner¹,

Saeed²,

Sommer³

et al. 1984

Hypertension

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“…It has been relatively difficult to demonstrate postjunctional M2-adrenoceptors in isolated arterial smooth muscle preparations although more success has been achieved with venous tissues (De Mey & Vanhoutte, 1980;1981;Shoji et al, 1983;Langer & Hicks, 1984). Using intact dog preparations, postjunctional a,-and x2-adrenoceptors have been identified in the forelimb (Cavero & Lefevre-Borg, 1981) and hindlimb Gardiner & Peters, 1982;Horn et al, 1982) vascular beds as well as the mesenteric and coronary (Holtz et al, 1982) circulations.…”

Section: Discussionmentioning

confidence: 99%

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

Berridge

Roach

1986

British J Pharmacology

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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.

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“…However, studies carried out on isolated organ preparations have shown that activation of a,-and x2-adrenoceptor subtypes summates to mediate vasoconstriction in a variety of organs including the ) The Macmillan Press Ltd 1987 hind limbs of the rat (Yamamoto et al, 1984), cat and dog (Gardiner & Peters, 1982); the cat lung (Hyman & Kadowitz, 1985) and rabbit kidney (Hesse & Johns, 1984; see also Ruffolo et al, 1981;. Meanwhile, other investigators have demonstrated a vasoconstriction primarily mediated by aI-adrenoceptors in the kidneys of the rat (Schmitz et al, 1981), dog (Horn et al, 1982;Wolff et al, 1984) and cat (Drew & Whiting, 1979) while vasoconstriction of the canine coronary vessels appears to be mediated selectively by a2-adrenoceptors (Kakihana et al, 1985).…”

Section: Introductionmentioning

confidence: 99%

Effects of α‐adrenoceptor agonists on cardiac output and its regional distribution in the pithed rat

Thomas

1987

British J Pharmacology

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ICardiac output, its distribution and tissue blood flows were determined with tracer microspheres in pithed rats during pressor responses elicited by either x,-adrenoceptor agonists (tirazoline, phenylephrine) or a2-adrenoceptor agonists (xylaxine, B-HT 933). Two doses were used for each of cirazoline and B-HT 933 and phenylephrine was investigated in the presence of propranolol (3 mg kg-'). The rats were pithed under halothane anaesthesia. 2 Cardiac output was increased by xylazine, the higher dose of B-HT 933 and phenylephrine. Heart rate was increased by phenylephrine and the higher doses of both cirazoline and B-HT 933. Stroke volume was greater in those groups given xylazine, phenylephrine and the higher dose of B-HT 933 but was decreased in those animals given the higher dose of cirazoline. 3 Both M2-adrenoceptor agonists increased the number of microspheres trapped in the lungs and the proportion ofthe cardiac output passing through the hepatic artery but decreased that flowing through the spleen and gastrointestinal tract. The higher dose of B-HT 933 also decreased the fraction of cardiac output fiowing to the kidneys but kidney blood flow was maintained as a result of the increased cardiac output. Also, this treatment reduced blood flow in the epididimal fat pads. 4 Both a,-adrenoceptor agonists increased the fraction of cardiac output received by the coronary vasculature but the only other effect on distribution common to these agents was an increase in the percentage of the cardiac output passing to the hepatic artery. Cirazoline decreased the proportion of cardiac output distributed to the gastrointestinal tract and spleen but the total fraction of cardiac output passing to the hepatosplanchnic region was maintained as a result of the increase to the hepatic artery.5 Cirazoline markedly reduced the proportion of the cardiac output received by the kidneys and absolute flow in these organs was only 1.4% of control after the higher dose of this agonist but flow at the lower dose was maintained by the higher cardiac output. 6 It is concluded that there is a significant contribution to the pressor responses elicited by x-agonists resulting from an oc-adrenoceptor-mediated increase in cardiac output that may result from greater heart rates or stroke volumes. Also, there is a differential distribution of cx-receptor subtypes throughout the vasculature which is especially noticeable in the kidneys.

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Postsynaptic α1- and α2-adrenoceptor involvement in the vascular responses to neuronally released and exogenous noradrenaline in the hindlimb of the dog and cat

Cited by 47 publications

References 17 publications

Sympathetic vasoconstriction sensitive to alpha 2-adrenergic receptor blockade. No evidence for preferential innervation of alpha 1-adrenergic receptors in the canine femoral bed.

Sympathetic vasoconstriction sensitive to alpha 2-adrenergic receptor blockade. No evidence for preferential innervation of alpha 1-adrenergic receptors in the canine femoral bed.

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

Effects of α‐adrenoceptor agonists on cardiac output and its regional distribution in the pithed rat

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