Identification of vascular postsynaptic alpha 1- and alpha 2-adrenoceptors in man.

Jie, K; Brummelen, P. Van; Vermey, P.; Timmermans, P.B.M.W.M.; Zwieten, P. A. van

doi:10.1161/01.res.54.4.447

Cited by 71 publications

(38 citation statements)

References 33 publications

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“…1843 These findings, together with the results from our study, indicate that also in humans postsynaptic a 2 -adrenergic (in addition to a,-adrenergic) receptors contribute substantially to the adrenergic sympathetic and humoral regulation of capacitance vessel tone. This would complement the role of this receptor type in the control of arteriolar tone in humans 13 and extend the evidence that sympathetic and humoral adrenergic activation act on two types of vascular a-adrenergic receptors, of which one (the vascular a 2 -adrenergic receptor) seems to be preferentially modulated by various physiological and pathophysiological factors.…”

supporting

confidence: 63%

Postsynaptic alpha 1- and alpha 2-adrenergic receptors in adrenergic control of capacitance vessel tone in vivo.

Elsner¹,

Stewart²,

Sommer³

et al. 1986

Hypertension

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SUMMARY The involvement of postsynaptic a 2 -adrenergic receptors in the adrenergic constriction of the capacitance vessels was studied in anesthetized, spontaneously breathing dogs under ganglionic blockade (hexamethonium, 10 mg/kg + 10 mg/kg/hr; methylatropine, 0.5 mg/kg). Effective vascular compliance was measured as an indicator of venous tone (blood volume was varied by ± 4 ml/kg in an 11-minute cycle of infusion, withdrawal, withdrawal, and reinfusion) and was calculated from the correlation between the observed changes in central venous pressure and the changes in blood volume. Sympathetic activity and central venous pressure were lower and effective vascular compliance was higher than values in untreated conscious dogs. The a 2 -agonist UK 14,304 (5-bromo-6-[imidazolin-2-ylamino]-quinoxaline; 0.04 and 0.12 //.g/kg/min; n = 6) dose-dependently lowered compliance and increased central venous pressure to levels found in conscious dogs, as did the ai-agonist methoxamine (10 and 30 ^ig/kg; n = 6). Rauwolscine (a 2 -antagonist), 0.3 mg/kg, significantly attenuated the effects of UK 14,304, but not those of methoxamine, while prazosin (a!-antagonist), 0.12 mg/kg, attenuated the effects of methoxamine, but not those of UK 14,304 (n = 6 each). Under /3-blockade (nadolol, 2 mg/kg; a = 12) venous tone was increased to about physiological levels by norepinephrine, 0.15 yug/kg/min i.v., or by neuronal norepinephrine release induced by tyramine, 10 /ng/kg/min i.v. These increases were significantly attenuated by prazosin as well as by rauwolscine and were abolished by a combination of both. These results indicate that postsynaptic a 2 -adrenergic receptors (in addition to a r adrenergic receptors) are functional in the venous system in vivo and contribute substantially to adrenergic sympathetic and humoral regulation of venous tone. (Hypertension 8: 1003(Hypertension 8: -1014(Hypertension 8: , 1986 KEY WORDS • total effective vascular compliance • venous tone • vascular a 2 -adrenergic receptors • capacitance vessel constriction • rauwolscine • prazosin A BNORMALITIES in venous function feature / \ prominently in the pathophysiological A. \ . changes found in various types of experimental hypertension 1 ' 2 as well as in hypertensive patients, 3 -4 and augmented venous tone is a key link underlying the postulated pathophysiological role of natriuretic hormone in hypertension.3 The abnormalities in venous function include increased sensitivity to

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supporting

confidence: 63%

Postsynaptic alpha 1- and alpha 2-adrenergic receptors in adrenergic control of capacitance vessel tone in vivo.

Elsner¹,

Stewart²,

Sommer³

et al. 1986

Hypertension

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“…48 Our finding that insulin, at plasma levels comparable to those observed in the postprandial state, attenuates selectively the increase in FVR induced by an a 2 -adrenergic agonist could indicate that the cross talk between the hormone and the sympathetic nervous system at the vascular level occurs through a well-identified vasoconstrictive signal transduction pathway. The observation that insulin infusion is able to abolish the reflex forearm vasoconstriction induced by graded LBNP during intra-arterial prazosin treatment supports this conclusion and may be in keeping with the hypothesis that a 2 -adrenergic receptors participate in the mediation of vasoconstriction elicited by increased endogenous catecholamine levels.…”

Section: Discussionmentioning

confidence: 71%

Insulin blunts sympathetic vasoconstriction through the alpha 2-adrenergic pathway in humans.

et al. 1994

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We investigated the mechanisms underlying the insulin-induced attenuation of sympathetic forearm vasoconstriction in healthy humans. In 5 subjects, we applied 20 mm Hg lower body negative pressure for 30 minutes in control conditions and during a 60-minute infusion of insulin (0.05 mU/kg per minute) in the brachiaJ artery and measured forearm norepinephrine kinetics and hemodynamics. In 11 subjects, we applied graded lower body negative pressure at 5, 10,15, and 20 mm Hg for 5 minutes each in control conditions and during the simultaneous intrabrachial administration of insulin (0.05 mU/kg per minute) (5 subjects) or insulin plus ouabain (3.5 fig/min per liter) (6 subjects) to investigate whether insulin acts through a potentiation of the vascular smooth muscle Na + ,K + -ATPase. To assess a possible effect of insulin on a specific adrenergic receptor pathway, in a further study group we evaluated (1) the forearm vascular response to intrabrachial infusion of the a,-adrenergic receptor agonist phenylephrine (0.5, 1, and 2 jig/kg per minute; n=7) and of the a 2 -adrenergic receptor agonist BHT-933 (0.5, 1, 2, and 4 jtg/kg per minute; n=9), and (2) the effects of intra-arterial infusion of prazosin (0.5 ^g/100 mL per minute) alone or combined with insulin on the forearm vascular response to

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“…In the present study the a,-adrenergic blocking effect of ketanserin was confirmed by the finding that it significantly reduced the vasoconstrictor response to the selective a,-agonist methoxamine. 49 Similar results were found for tyramine, which acts as an indirect agonist of a-adrenergic receptors by displacing norepinephrine from the sympathetic nerve endings, 50 ' 5I thus providing evidence that ketanserin also is able to counteract a vasoconstrictor response induced by endogenously released norepinephrine. Although the a r blocking effect of ketanserin has been regarded as weak by several investigators, 23 ' 52~54 the present study clearly showed that this effect of ketanserin in this particular vascular bed occurred at lower doses than are needed for 5-HT 2 blockade (see Figures 5 and 6).…”

mentioning

confidence: 60%

Regional vascular effects of serotonin and ketanserin in young, healthy subjects.

et al. 1988

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SUMMARY The local hemodynamic effects of serotonin (5-hydroxytryptamine; 5-HT) and the selective 5-HT 2 antagonist ketanserin were investigated in the forearm of 20 healthy volunteers. Single doses of 5-HT (0.1-80 ng/kg/min) and ketanserin (5-125 ng/kg/min) were administered intra-arterially. The relative a,-adrenergic receptor and 5-HT 2 blocking potencies of ketanserin were investigated using intra-arterial infusions of cumulative doses of methoxamine (0.1, 0.3, and 0.5 jiig/kg/min), tyramine (0.25, 0.50, and 1.25 /xg/kg/min), and 5-HT (10, 30, and 80 ng/kg/min) together with a low dose (5 ng/kg/min) and a high dose (50 ng/kg/min) of ketanserin. Forearm blood flow was measured by venous occlusion plethysmography. Heart rate and intra-arterial blood pressure were recorded semicontinuously. Intra-arterial infusion of 5-HT induced an initial transient vasodilatation, followed by a steady vasodilatation for the low doses of 5-HT (0.1-10 ng/kg/min; p < 0.05). A steady vasoconstriction was only obtained at the highest dose of 5-HT. Ketanserin induced a dose-dependent increase in forearm blood flow from 15 ng/kg/min (p < 0.05) onward. The vasodilatation induced by 5-HT (1 ng/kg/min) was significantly enhanced by ketanserin (125 ng/kg/min; p < 0.05), whereas the vasoconstriction elicited by 5-HT (80 ng/kg/min) was reversed by ketanserin (50 ng/kg/min; p < 0.05), thus confirming that 5-HT 2 receptors were stimulated by 5-HT. In this model ketanserin proved to be a more potent antagonist of a r adrenergic receptors than of 5-HT 2 receptors, since the vasoconstriction induced by methoxamine and tyramine was reduced by a lower dose of ketanserin than was the vasoconstriction induced by 5-HT. It is concluded that 5-HT acts predominantly as a vasodilator in healthy subjects, probably by 5-HT,-like receptor stimulation. Only at high doses of 5-HT did vasoconstriction mediated by 5-HT 2 receptor stimulation occur. The vasodilatation induced by ketanserin was due most likely to its a r adrenergic blocking properties. (Hypertension 11: 256-263,1988

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Identification of vascular postsynaptic alpha 1- and alpha 2-adrenoceptors in man.

Cited by 71 publications

References 33 publications

Postsynaptic alpha 1- and alpha 2-adrenergic receptors in adrenergic control of capacitance vessel tone in vivo.

Postsynaptic alpha 1- and alpha 2-adrenergic receptors in adrenergic control of capacitance vessel tone in vivo.

Insulin blunts sympathetic vasoconstriction through the alpha 2-adrenergic pathway in humans.

Regional vascular effects of serotonin and ketanserin in young, healthy subjects.

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