Effects of adenosine a2a receptor agonist, cgs 21680, on blood pressure, cardiac index and arterial conductance in anaesthetized rats

Nekooeian, Ali Akbar; Tabrizchi, Reza

doi:10.1016/0014-2999(96)00250-6

Cited by 28 publications

(35 citation statements)

References 25 publications

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“…However, systemic administration of selective A 2A R agonists can increase HR, probably due to reflex activation secondary to reduced blood pressure (6,31,32,34,35). In addition, there is evidence that there are ARs in the brain stem regulating cardiovascular control centers (2)(3)(4).…”

Section: Discussionmentioning

confidence: 99%

Physiological roles of A₁ and A_2A adenosine receptors in regulating heart rate, body temperature, and locomotion as revealed using knockout mice and caffeine

Yang

Chen²,

Fredholm³

2009

American Journal of Physiology-Heart and Circulatory Physiology

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Yang JN, Chen JF, Fredholm BB. Physiological roles of A1 and A2A adenosine receptors in regulating heart rate, body temperature, and locomotion as revealed using knockout mice and caffeine. Am J Physiol Heart Circ Physiol 296: H1141-H1149, 2009. First published February 13, 2009 doi:10.1152/ajpheart.00754.2008.-Heart rate (HR), body temperature (Temp), locomotor activity (LA), and oxygen consumption (O2C) were studied in awake mice lacking one or both of the adenosine A 1 or A2A receptors (A1R or A2AR, respectively) using telemetry and respirometry, before and after caffeine administration. All parameters were lower during day than night and higher in females than males. When compared with wild-type (WT) littermates, HR was higher in male A 1R knockout (A1RKO) mice but lower in A2ARKO mice and intermediate in A1-A2AR double KO mice. A single dose of an unselective ␤-blocker (timolol; 1 mg/kg) abolished the HR differences between these genotypes. Deletion of A 1Rs had little effect on Temp, whereas deletion of A 2ARs increased it in females and decreased it in males. A 1-A2ARKO mice had lower Temp than WT mice. LA was unaltered in A 1RKO mice and lower in A 2ARKO and A1-A2ARKO mice than in WT mice. Caffeine injection increased LA but only in mice expressing A 2AR. Caffeine ingestion also increased LA in an A 2AR-dependent manner in male mice. Caffeine ingestion significantly increased O 2C in WT mice, but less in the different KO mice. Injection of 30 mg/kg caffeine decreased Temp, especially in KO mice, and hence in a manner unrelated to A 1R or A 2AR blockade. Selective A2B antagonism had little or no effect. Thus A 1R and A2AR influence HR, Temp, LA, and O2C in mice in a sex-dependent manner, indicating effects of endogenous adenosine. The A2AR plays an important role in the modulation of O2C and LA by acute and chronic caffeine administration. There is also evidence for effects of higher doses of caffeine being independent of both A 1R and A2AR. diurnal rhythm; metabolic rate; locomotor activity; adenosine; telemetry CAFFEINE (1,3,7-trimethylxanthine), the most widely consumed stimulant in the world, acts as a competitive antagonist of adenosine receptors (ARs) (18). It is much more potent on three of the known receptors, A 1 , A 2A , and A 2B (A 1 R, A 2A R, and A 2B R, respectively) than on the fourth, the A 3 R (17). Since a competitive antagonist will have effects only when and where receptors are activated by an agonist, it is relevant that endogenous agonist adenosine is more potent on A 1 R and A 2A R than on A 2B R. The potency of adenosine as an agonist in addition depends on the density of the receptors (16). The levels of adenosine are low under physiological condition but are sufficient to partially activate A 1 R, A 2A R, and A 3 Rs where the receptors are abundantly expressed. For these reasons caffeine is generally believed to act on A 1 R and A 2A R to exert most of its effects, at least when given in lower doses (18). However, a recent study showed that A 2B R knockout (A 2B RKO) mice have e...

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Section: Discussionmentioning

confidence: 99%

Physiological roles of A₁ and A_2A adenosine receptors in regulating heart rate, body temperature, and locomotion as revealed using knockout mice and caffeine

Yang

Chen²,

Fredholm³

2009

American Journal of Physiology-Heart and Circulatory Physiology

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“…In animals as well as humans, adenosine and its analogs cause sinus tachycardia and lower systemic blood pressure (Biaggioni et al, 1987;Lappe et al, 1992;Bonizzoni et al, 1995;Alberti et al, 1997;Koos and Chau, 1998;Barrett et al, 2005;Hendel et al, 2005;Schindler et al, 2005). The sinus tachycardia has been attributed to the baroreceptor reflex caused by the decrease in arterial pressure (Webb et al, 1990(Webb et al, , 1991Nekooeian and Tabrizchi, 1996;Alberti et al, 1997). However, there is also evidence that adenosine-mediated tachycardia can occur independent of a decrease in MAP (Lappe et al, 1992;Mathot et al, 1995;Koos and Chau, 1998;Schindler et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…The peripheral vasodilation causes a decrease in arterial pressure, which in turn elicits a baroreflex-mediated activation of the sympathetic nervous system (SNS) and thereby an increase in heart rate. This has been proposed to be the mechanism underlying the increase in heart rate (HR) caused by adenosine and A 2A receptor agonists (Nekooeian and Tabrizchi, 1996;Alberti et al, 1997). However, it has been shown that adenosine elicits a direct positive chronotropic effect (Koos et al, 1993) and that activation of A 2A receptors leads to direct stimulation of the autonomic nervous system (Koos and Chau, 1998).…”

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confidence: 99%

Tachycardia Caused by A_2A Adenosine Receptor Agonists Is Mediated by Direct Sympathoexcitation in Awake Rats

Dhalla¹,

Wong²,

Wang³

et al. 2005

J Pharmacol Exp Ther

105

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Adenosine-induced tachycardia is suggested to be mediated via A 2A receptors; however, the exact mechanism for this effect remains to be understood. The present study was carried out using regadenoson, a selective A 2A adenosine receptor agonist, to determine the role of the A 2A receptor subtype in adenosine-induced tachycardia. Regadenoson (0.3-50 g/kg) given as a rapid i.v. bolus to awake rats caused a dosedependent increase in heart rate (HR). Mean arterial pressure (MAP) increased at lower doses, whereas at higher doses, there was a decrease in MAP. The increase in HR was evident at the lowest dose (0.3 g/kg) of regadenoson at which there was no appreciable decrease in MAP. Pretreatment with 30 g/kg, an A 2A receptor antagonist, attenuated the decrease in MAP and the increase in HR caused by regadenoson. Pretreatment with metoprolol (1 mg/ kg), a ␤-blocker, attenuated the increase in HR but had no effect on the hypotension caused by regadenoson. In the presence of hexamethonium (10 mg/kg), a ganglionic blocker, the tachycardia was completely prevented even though MAP was further reduced. Regadenoson treatment (10 g/kg) significantly (p Ͻ 0.05) increased plasma norepinephrine levels almost 2-fold above baseline. The dissociation of HR and MAP effects by dose, time, and pharmacological interventions provides evidence that tachycardia caused by regadenoson is independent of the decrease in MAP and may not entirely be baroreflex-mediated, suggesting that regadenoson may cause a direct stimulation of the sympathetic nervous system via activation of A 2A adenosine receptors.

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“…In our previous investigation, dexamethasone also inhibited iNOS following hemorrhage in thiobutabarbital-anesthetized rats (22). It is recognized that under normal circumstances an increase in arterial resistance (afterload) can result in a reduction in cardiac output which occurs due to increased impedance to flow (23). Moreover, a reduction in arterial resistance can result in the opposite effect and thus increase cardiac output under normal, as well as, pathophysiological conditions (24,25).…”

Section: Discussionmentioning

confidence: 91%

The Influence of Phosphodiesterase Inhibitor, Rolipram, on Hemodynamics in Lipopolysaccharide-Treated Rats

Dutta

Ryan

Tabrizchi

2001

Japanese Journal of Pharmacology

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ABSTRACT-Administration of bacterial endotoxin (lipopolysaccharide, LPS) intravenously has been noted to produce a shock state, which is characterized by hypotension and mutli-organ system failure. The aim of the present investigation was to (a) examine the influence of rolipram on hemodynamics, plasma levels of tumor necrosis factor-a (TNF-a) levels, and production of inducible nitric oxide synthase (iNOS) in the lungs, ex vivo, in LPS-treated rats, and (b) determine the cardiovascular effects of a selective a1-adrenoceptor agonist, methoxamine, in the absence or presence of rolipram in rats treated with LPS. Blood pressure, cardiac index, heart rate and arterial resistance were assessed in Long-Evans rats anesthetized with thiobutabarbital. Administration of LPS to animals resulted in a significant reduction in cardiac index over time. The administration of LPS to rats resulted in a substantial rise in the plasma levels of TNF-a. Furthermore, the injection of LPS resulted in a significant increase in the iNOS activity in the lungs. Pre-treatment with rolipram prevented the decline in cardiac index in animals that received LPS. Infusion of methoxamine into animals injected with rolipram and pre-treated with LPS did not result in significant changes in cardiac index. Pre-treatment with rolipram or dexamethasone in animals injected with LPS significantly prevented the rise in TNF-a when compared to the respective values in vehicle-treated animals. Our present observations support the view that the cardiac index can be maintained in animals treated with LPS independent of iNOS inhibition.

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Effects of adenosine a2a receptor agonist, cgs 21680, on blood pressure, cardiac index and arterial conductance in anaesthetized rats

Cited by 28 publications

References 25 publications

Physiological roles of A₁ and A_2A adenosine receptors in regulating heart rate, body temperature, and locomotion as revealed using knockout mice and caffeine

Physiological roles of A₁ and A_2A adenosine receptors in regulating heart rate, body temperature, and locomotion as revealed using knockout mice and caffeine

Tachycardia Caused by A_2A Adenosine Receptor Agonists Is Mediated by Direct Sympathoexcitation in Awake Rats

The Influence of Phosphodiesterase Inhibitor, Rolipram, on Hemodynamics in Lipopolysaccharide-Treated Rats

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Effects of adenosine a2a receptor agonist, cgs 21680, on blood pressure, cardiac index and arterial conductance in anaesthetized rats

Cited by 28 publications

References 25 publications

Physiological roles of A1 and A2A adenosine receptors in regulating heart rate, body temperature, and locomotion as revealed using knockout mice and caffeine

Physiological roles of A1 and A2A adenosine receptors in regulating heart rate, body temperature, and locomotion as revealed using knockout mice and caffeine

Tachycardia Caused by A2A Adenosine Receptor Agonists Is Mediated by Direct Sympathoexcitation in Awake Rats

The Influence of Phosphodiesterase Inhibitor, Rolipram, on Hemodynamics in Lipopolysaccharide-Treated Rats

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Product

Resources

About

Physiological roles of A₁ and A_2A adenosine receptors in regulating heart rate, body temperature, and locomotion as revealed using knockout mice and caffeine

Physiological roles of A₁ and A_2A adenosine receptors in regulating heart rate, body temperature, and locomotion as revealed using knockout mice and caffeine

Tachycardia Caused by A_2A Adenosine Receptor Agonists Is Mediated by Direct Sympathoexcitation in Awake Rats