Adenosine Attenuates the Vasoconstrictor Response to the Cold Pressor Test in Humans

Smits, Paul; Jw, Lenders; Jj, Willemsen; Ja, den Arend; Thien, Theo

doi:10.1097/00005344-199106000-00024

Cited by 6 publications

(6 citation statements)

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“…4,5,7,[20][21][22]24 The mechanism responsible for increased levels of ADO in the contralateral arm is presumably different. Following the CPT, levels of ADO are significantly higher in the tested than in the contralateral arm.…”

Section: Discussionmentioning

confidence: 99%

“…The increase in extracellular ADO in the tested arm following the CPT may be due to its enhanced production in ischaemic tissue, [7][8][9]14 but may also be an expression of increased sympathoexcitatory tone due to augmented NA release. 4,5,7,[20][21][22]24 The mechanism responsible for increased levels of ADO in the contralateral arm is presumably different. Because the half-life of ADO is very short, [35][36][37] the increase in ADO levels observed in the arm not undergoing the CPT is unlikely to be mainly an expression of augmented ADO release in the tested arm.…”

Section: Discussionmentioning

confidence: 99%

“…The nucleoside evokes a sympathoexcitatory reflex by stimulating chemically sensitive receptors and central nervous system (CNS) afferent fibres in the kidney, 18 heart 19 and skeletal muscle. 4,5,7,24 In contrast, ADO also modulates NA release at nerve endings in a dose-dependent fashion by acting on A1 (inhibitory) 25,26 and A2 (facilitatory) 27 adenosine receptors. 4,5,7,24 In contrast, ADO also modulates NA release at nerve endings in a dose-dependent fashion by acting on A1 (inhibitory) 25,26 and A2 (facilitatory) 27 adenosine receptors.…”

Section: Introductionmentioning

confidence: 99%

“…16,17 More recently, evidence has been provided that ADO also has a dual action on the SNS in conscious humans. 7,[20][21][22][23] This reflex is elicited in the course of locally provoked ischaemia in the forearm, 4,5,7,24 leading to the release of noradrenaline (NA) 7,24 with an increase in arterial blood pressure and heart rate. 7,[20][21][22][23] This reflex is elicited in the course of locally provoked ischaemia in the forearm, 4,5,7,24 leading to the release of noradrenaline (NA) 7,24 with an increase in arterial blood pressure and heart rate.…”

Section: Introductionmentioning

confidence: 99%

“…The nucleoside evokes a sympathoexcitatory reflex by stimulating chemically sensitive receptors and central nervous system (CNS) afferent fibres in the kidney, 18 heart 19 and skeletal muscle. 7,[20][21][22][23] This reflex is elicited in the course of locally provoked ischaemia in the forearm, 4,5,7,24 leading to the release of noradrenaline (NA) 7,24 with an increase in arterial blood pressure and heart rate. 4,5,7,24 In contrast, ADO also modulates NA release at nerve endings in a dose-dependent fashion by acting on A1 (inhibitory) 25,26 and A2 (facilitatory) 27 adenosine receptors.…”

Section: Introductionmentioning

confidence: 99%

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Systemic Adenosine Increase During Cold Pressor Test Is Dependent on Sympathetic Activation

Laghi-Pasini

Capecchi

Colafati³

et al. 1999

Clin Exp Pharma Physio

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1. Following local vasoconstriction-inducing stimuli, such as the cold pressor test (CPT), significant changes occur in haemodynamics, with a rise in arterial blood pressure and heart rate (HR) due to the activation of the sympathetic nervous system. Among the compensatory mechanisms to local ischaemia, the endogenous nucleoside adenosine (ADO) has been suggested to play a relevant role by contributing to sympathetic stimulation. The possibility was investigated that CPT-induced increases in plasma ADO levels were not only an expression of the increased production of ADO in the ischaemic area, but also a consequence of systemic sympathoexcitatory mechanisms, thus showing a bidirectional involvement of the mechanisms of ADO formation. 2. The CPT was performed in 15 volunteers and mean arterial blood pressure (MABP) and HR were evaluated, together with plasma levels of noradrenaline (NA) and ADO in the tested and contralateral arm. The 15 subjects were then divided into three groups of five that were treated with either 5 mg transdermal clonidine weekly, 100 mg atenolol daily or 600 mg aminophylline twice daily. After 1 week treatment, the same test was repeated in the respective groups. 3. The CPT induced a rise in MABP and HR and an increase in plasma levels of NA and ADO. Increases in ADO were more pronounced in the tested arm. Clonidine blunted the haemodynamic response and NA release, while increases in ADO increase were reduced to a greater extent in the contralateral arm rather than the tested arm. Atenolol only affected MABP and HR without any effect on NA and ADO levels. Theophylline did not show any effect on CPT-induced changes. 4. In conclusion, local vasoconstriction and ischaemia induced in one arm following CPT are associated with haemodynamic changes dependent on the activation of the sympathetic system. The observed increase in plasma levels of ADO seems to be, in part, a direct expression of local responses to ischaemia (pre-dominant in the tested arm), but also appears as the consequence of systemic sympathoexcitatory mechanisms. Such increases in ADO are not dependent on a beta 1-adrenoceptor-mediated mechanism. Finally, theophylline, at a therapeutic dose, has no effect on the response to CPT.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…The nucleoside evokes a sympathoexcitatory reflex by stimulating chemically sensitive receptors and central nervous system (CNS) afferent fibres in the kidney, 18 heart 19 and skeletal muscle. 7,[20][21][22][23] This reflex is elicited in the course of locally provoked ischaemia in the forearm, 4,5,7,24 leading to the release of noradrenaline (NA) 7,24 with an increase in arterial blood pressure and heart rate. 4,5,7,24 In contrast, ADO also modulates NA release at nerve endings in a dose-dependent fashion by acting on A1 (inhibitory) 25,26 and A2 (facilitatory) 27 adenosine receptors.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Systemic Adenosine Increase During Cold Pressor Test Is Dependent on Sympathetic Activation

Laghi-Pasini

Capecchi

Colafati³

et al. 1999

Clin Exp Pharma Physio

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Cardiovascular effects of sulphonylurea derivatives

Smits

Thien²

1995

Diabetologia

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Cardiovascular effects of sulphonylurea derivatives

Smits

1997

Diabetologia

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The classical sulphonylurea derivative glibenclamide is widely prescribed for the treatment of non-insulindependent diabetes mellitus (NIDDM). The mechanism of action of this drug is based on an augmented release of insulin from the beta cells of the pancreas, triggered by the closing of so-called ATP-dependent potassium channels (ATP: adenosine'5-triphosphate) [1]. This ultimately results in an influx of calcium via opening of voltage-dependent calcium-ion channels, and the subsequent binding of calcium ions to calmodulin triggers the exocytosis of insulin-containing secretory granules. The central issue of this presentation is the fact that the occurrence of K ATP -channels is not restricted to the pancreatic beta cells. These particular ion channels occur in several organ systems, including the cardiovascular system [2,3].The open state probability of K ATP -channels is dependent on the cytosolic concentration of ATP. During hypoxia and/or ischaemia, the cytosolic concentration of ATP falls which directly results in opening of K ATP -channels. The subsequent efflux of potassium induces hyperpolarization of the cell membrane which shortens the action potential in the myocardial cell leading to a reduction in the contractile amplitude of myocardial cells. In vascular smooth muscle cells, opening of K ATP -channels and subsequent hyperpolarization exerts relaxation of these cells, resulting in an obvious vasodilator response.The vascular smooth muscle cell K ATP -channels can be opened pharmacologically by potassium-channel-opening drugs such as cromakalim and the classical vasodilator drug diazoxide [3]. Glibenclamide is able to reduce the vasodilator response to these K ATP channel-opening drugs, indicating the ability to block vascular K ATP -channels. Apart from the interaction with K ATP -channel-opening drugs, glibenclamide has also been reported to inhibit the vasodilator response to adenosine, and to (endothelium-dependent) vasodilators such as acetylcholine, vasoactive intestinal peptide and insulin [4]. Also in the myocardial cell, glibenclamide is able to reduce the response to K ATP -channel-opening agents [4].Animal experiments have shown that the ischaemia-induced opening of myocardial K ATP -channels is an endogenous cardioprotective mechanism against ischaemia and reperfusion damage. In several ischaemia models glibenclamide increased infarct size [5,6]. On the other hand blockade of the sulphonylurea receptor is associated with a reduction in ischaemia-related arrhythmias [4]. Not only myocardial K ATPchannels are involved in the response to ischaemia. Other investigators have demonstrated that the vascular smooth muscle cell response to ischaemia is also inhibited by sulphonylurea derivatives, represented by a reduction of the post-occlusive hyperaemic response after pretreatment with glibenclamide.Interestingly, the newly developed sulphonylurea derivative glimepiride seems to act more selectively, since its hypoglycaemic action is more pronounced than that of glibenclamide, whereas animal dat...

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Adenosine Attenuates the Vasoconstrictor Response to the Cold Pressor Test in Humans

Cited by 6 publications

References 0 publications

Systemic Adenosine Increase During Cold Pressor Test Is Dependent on Sympathetic Activation

Systemic Adenosine Increase During Cold Pressor Test Is Dependent on Sympathetic Activation

Cardiovascular effects of sulphonylurea derivatives

Cardiovascular effects of sulphonylurea derivatives

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