Alpha‐adrenergic receptors in human blood vessels.

Brummelen, P. Van; Jie, K; Zwieten, PA van

doi:10.1111/j.1365-2125.1986.tb02851.x

Cited by 48 publications

(39 citation statements)

References 26 publications

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“…In human vasculature, locally released norepinephrine (by lower body negative pressure and by tyramine infusion) has a different functional effect than infused norepinephrine. 36 Apparently the released norepinephrine preferentially activates postsynaptic a,-receptors, whereas norepinephrine infusion also activates vasoconstrictive extrajunctional a 2 -receptors. 37 This functional difference in the patterns of receptor activation with endogenous versus exogenous norepinephrine permits the postulation of different mechanisms by which physiological vasoconstriction may have a larger effect than the vasoconstriction with infused norepinephrine.…”

Section: Discussionmentioning

confidence: 98%

Vasoconstriction with norepinephrine causes less forearm insulin resistance than a reflex sympathetic vasoconstriction.

et al. 1994

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We used the insulin-perfused human forearm model to assess the effects of vasoconstriction induced with norepinephrine on the extraction of glucose in the forearm in two groups of healthy young volunteers. The norepinephrine findings were compared with a previously studied group in which vasoconstriction had been caused by reflex activation of the sympathetic nervous system. The aim of the study was to determine the relative importance of hemodynamic and receptor-mediated mechanisms of insulin resistance. Plasma insulin, arterial and venous glucose samples, and forearm blood flow were measured at 10-minute intervals during a 30-minute baseline, a 60-minute intra-arterial insulin infusion, and during 30 minutes of insulin infusion plus vasoconstriction. Group 1 (n=14) had physiological vasoconstriction induced by inflation of bilateral thigh cuffs to 40 mm Hg to cause pooling of blood in the lower extremities and reflex vasoconstriction in the forearm; group 2 (n=8) had intra-arterial infusion of norepinephrine to achieve the same degree of vasoconstriction as seen with inflation of thigh cuffs in group 1. Subjects in A frequent association of tissue insulin insensitivity and blood pressure in humans has been ob-L. served in several clinical surveys.17 Recent investigations have focused on a possible pressor effect of insulin through sympathetic nervous system tone, 811 an increase in the intravascular volume, 12 -13 or through the effect of insulin on vascular smooth muscle.14 ' 15 It has been speculated that high insulin in insulin-resistant states may cause the increase of blood pressure in hypertension through these various pressor mechanisms. 16 In contrast to the insulinogenic hypothesis of the blood pressure elevation, the infusion of insulin into humans has been repeatedly associated with vasodilation or attenuation of vasoconstrictive stimuli instead of a pressor effect.11 . 1719In a recent review we offered an alternative explanation for the frequent association between elevated blood pressure and insulin resistance. 20 ' 21 We proposed that vascular changes in the microcirculation secondary to long-standing elevations in blood pressure may alter the delivery of insulin and glucose to tissues and may thereby, in part, cause insulin resistance. Our hypothesis suggests that the primary defect may be vascular in nature, from elevation in blood pressure, and not in tissue sensitivity to the effects of insulin. A first step group 3 (n=7) had infusion of intra-arterial norepinephrine to achieve a twofold increase in physiological vasoconstriction. With a physiological decrease in forearm blood flow (group 1), there was a 19% decrease in forearm blood flow resulting in a 23% reduction in glucose uptake in the forearm (P<.03). The same degree of reduction in forearm blood flow with a predominantly a-adrenergic agonist, norepinephrine (group 2), causes much less insulin resistance (a decrease in utilization of 13%) (P

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Section: Discussionmentioning

confidence: 98%

Vasoconstriction with norepinephrine causes less forearm insulin resistance than a reflex sympathetic vasoconstriction.

et al. 1994

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“…AI immediately reduced CBF and CVC, with little doubt as a result of a-adrenoreceptor-induced vasoconstriction in the skin (Edholm et at. 1956;Whelan, 1967;Van Brummelen et al 1986). These decreases in CBF and CVC were accompanied by a transient decline in skin temperature (n.s.)…”

Section: Discussionmentioning

confidence: 99%

Plasma catecholamines and hyperglycaemia influence thermoregulation in man during prolonged exercise in the heat.

Mora-Rodríguez

González‐Alonso

Below

et al. 1996

The Journal of Physiology

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1. We manipulated plasma catecholamines (combined adrenaline and noradrenaline concentrations) to three levels during prolonged exercise to determine their effect on cutaneous and forearm vascular conductance (CVC and FVC), oesophageal temperature (T..) and cardiovascular responses.2. On three occasions, seven endurance-trained men cycled at 65% V2, max in the heat (33 1 + 0 7°C) for 120-150 min. During the control trial (150 min duration), 0 45% saline was intravenously infused (SI) starting at 30 min, at a rate that replaced a third of the fluid losses. The infusion start time and rate were identical in all three trials. During SI, plasma catecholamine levels increased progressively and were 18&2 + 2 7 pmol ml-1 at 150 min. In another trial (120 min duration), adrenaline was infused (AI) at 0 1 jug kg-1 min-' and plasma catecholamine levels were elevated 6 pmol ml-' above SI during the 60-120 min period. In a third trial (150 min duration), an 18% glucose solution was infused (GI) at a rate that maintained plasma glucose levels above 11 mm and plasma catecholamine levels were 5 0-5 5 pmol ml-' lower (P < 0'05) than SI from 120-150 min.3. Heat production and sweat rate were not different during the three trials and neither was the decline in stroke volume, cardiac output and mean arterial pressure.4. Soon after beginning AI, CVC decreased 15%, TRes increased by 04 + 0.1°C and heart rate increased by 6 + 1 beats min-; these significant (P < 0 05) differences from SI were maintained throughout the bout. As a result of GI, FVC was 15% higher than SI and TRe and heart rate were attenuated by 0 3 + 0.1°C and 7 + 1 beats min-' at 150 min compared with SI (P < 0'05).5. In conclusion, large increases in plasma catecholamine levels cause hyperthermia during exercise by vasoconstricting the skin. The mechanisms by which hyperglycaemia (i.e. 11 mM) attenuates hyperthermia are less clear and may be due to others factors besides attenuation of the plasma catecholamine response to exercise.The cutaneous circulation in humans is one of the major routes for heat dissipation during exercise in the heat and is affected by many factors including local temperature, circulating autacoids and hormones, and nervous system reflexes (Rowell, 1986). The cutaneous vasculature lacks fl-adrenergic receptors but is richly supplied with a-receptors that cause vasoconstriction when stimulated. a-Adrenergic vasoconstriction can be induced either by noradrenaline released from sympathetic vasoconstrictor nerve endings in the skin or by plasma catecholamines (Rowell, 1986).It is not well understood how vasodilatation occurs in the non-acral cutaneous vasculature. Substantial vasodilatation, beyond that which occurs with just the withdrawal of sympathetic vasoconstrictor tone when core temperature increases, is termed active vasodilatation. Active vasodilatation is considered to be an active process because it requires an intact sympathetic innervation to the skin (Edholm, Fox & Macpherson, 1957), but the specific neurotransmitter and underlyi...

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“…Secondly, although there is now convincing evidence that post-junctional vascular a2-adrenoceptors are involved in the regulation of vascular tone in humans (Van Brummelen et al, 1986) stimulation of the 'classical' vascular a1-adrenoceptors appears to remain the major determinant of systemic vascular resistance. It is therefore conceivable that, at least at high infusion rates, a-methylnoradrenaline loses its relative a2-vs a1-selectivity and may also stimulate vascular a1-adrenoceptors.…”

Section: Discussionmentioning

confidence: 99%

“…There is some evidence that pre-junctional a2-adrenoceptors are involved in the regulation of noradrenaline release in man (Brown et al, 1985;Jie et al, 1987) and that post-junctional a2-adrenoceptors may contribute to the regulation of human peripheral vascular tone (van Brummelen et al, 1986). In addition it has been reported that post-junctional a2-adrenoceptor mediated vasoconstriction is enhanced in essential hypertension (Bolli et al, 1984).…”

Section: Introductionmentioning

confidence: 99%

An evaluation of the alpha‐adrenoceptor antagonism produced by SK&F 86466 in healthy normotensive males.

Schafers

Elliott

Howie

et al. 1990

Brit J Clinical Pharma

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SK&F 86466 is a novel, potent a-adrenoceptor antagonist which, in animal experiments, is reported to show a high selectivity for a2-adrenoceptors at both pre-and postjunctional sites. The effects of two intravenous doses of 80 and 200 pLg kg-' of SK&F 86466were assessed in a placebo-controlled, double-blind, randomised study in eight young, healthy, normotensive males. Two indices of a-adrenoceptor activity were investigated: i) Pressor responsiveness to the relatively selective ox-adrenoceptor agonist phenylephrine and to the preferential ot2-adrenoceptor agonist oa-methylnoradrenaline. ii) Circulating levels of noradrenaline. SK&F 86466 at a dose of 200,ug kg-1 produced rightward shifts of the pressor dose-response curves to both agonists: a 1.4 fold shift for phenylephrine (P = 0.023) and a 1.6 fold shift for a-methylnoradrenaline (P = 0.051). Erect plasma noradrenaline sampled at 105 min into the infusion was significantly increased from 2.9 to 5.0 nmol 1-1 by SK&F 86466 200 ,ug kg-' (P = 0.002). The change in the phenylephrine responses indicates post-junctional al-adrenoceptor blockade and the rise in noradrenaline is consistent with pre-junctional a2-adrenoceptor antagonist activity. Overall the results of this study suggest that SK&F 86466, at a dose of 200 jig kg-', causes both oxl-and aL2-adrenoceptor antagonism in human subjects.

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Alpha‐adrenergic receptors in human blood vessels.

Cited by 48 publications

References 26 publications

Vasoconstriction with norepinephrine causes less forearm insulin resistance than a reflex sympathetic vasoconstriction.

Vasoconstriction with norepinephrine causes less forearm insulin resistance than a reflex sympathetic vasoconstriction.

Plasma catecholamines and hyperglycaemia influence thermoregulation in man during prolonged exercise in the heat.

An evaluation of the alpha‐adrenoceptor antagonism produced by SK&F 86466 in healthy normotensive males.

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