Adenosine and adenosine antagonism in asthma

The effects of the ATP-sensitive K(+)-channel blocker glibenclamide on the cardiovascular responses to adenosine in dogs were determined. Adenosine (0.01-20 mumol/kg iv) caused coronary vasodilatation, arterial hypotension, and bradycardia in dogs with either combined beta-adrenergic and muscarinic receptor blockade or with bilateral cervical vagotomy plus beta-adrenergic receptor blockade. The 50% effective dose for adenosine-induced coronary dilatation was increased from 0.13 +/- 0.04 mumol/kg in the control state to 1.1 +/- 0.5 mumol/kg after 2 mg/kg of glibenclamide (P less than 0.001). Adenosine at 5 mumol/kg reduced heart rate by 19 +/- 5% from a baseline of 158 +/- 6 beats/min in five anesthetized dogs. After glibenclamide (10 mg/kg), this dose of adenosine failed to cause a significant change in heart rate. The arterial hypotensive effects of adenosine were also attenuated by glibenclamide. Thus glibenclamide inhibited adenosine-induced bradycardia, hypotension, and coronary dilatation. On the other hand, glibenclamide did not affect the reductions in heart rate caused by vagus nerve stimulation. The mechanism of this adenosine antagonism is not known but, in the case of bradycardia, it does not appear to involve any of the steps shared in common by both adenosine-induced and vagal responses of the sinoatrial node.

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Adenosine antagonism decreases metabolic but not functional recovery from ischemia

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1991.260.1.h193 ◽

1991 ◽

Vol 260 (1) ◽

pp. H193-H200 ◽

Cited By ~ 5

Author(s):

D. A. Angello ◽

J. P. Headrick ◽

N. M. Coddington ◽

R. M. Berne

Keyword(s):

Functional Recovery ◽

Left Ventricular ◽

Low Flow ◽

Ischemia And Reperfusion ◽

Constant Flow ◽

Hemodynamic Parameters ◽

Isolated Hearts ◽

Rat Hearts ◽

Adenosine Antagonism ◽

Developed Pressure

The effect of adenosine receptor antagonism on function and metabolism was examined in isolated hearts during low flow ischemia and reperfusion. Isovolumic rat hearts perfused at constant flow were subjected to 30 min of ischemia followed by 30 min of reperfusion. Infusion of vehicle or 10 microM 8-phenyltheophylline (8-PT) was initiated 10 min before ischemia and maintained throughout reperfusion. 8-PT infusion had no significant effects on hemodynamic parameters or metabolism preischemia. During ischemia, left ventricular developed pressure declined to approximately 15% of preischemic values in control and 8-PT hearts, and ATP and PCr decreased to approximately 73 and 60% of preischemic values. Inorganic phosphate (Pi) increased to 353 = 41 and 424 +/- 53% of preischemic values in control and 8-PT hearts, respectively. After reperfusion, function recovered to greater than 95% of preischemic levels in control and 8-PT hearts. Unlike control hearts, recovery of metabolites was significantly different during reperfusion in 8-PT hearts (P less than 0.05); ATP, phosphocreatine, and Pi recovered to 82 +/- 8, 71 +/- 8, and 281 +/- 27% of preischemic values, respectively. Venous purine washout was significantly greater (P less than 0.05) during reperfusion in 8-PT hearts (327 +/- 113 nmol) than in control hearts (127 +/- 28 nmol). Blockade of adenosine receptors appears to adversely affect metabolic but not functional recovery in the ischemic-reperfused myocardium.

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Endogenous adenosine modulates alpha 2- but not alpha 1-adrenergic constriction of coronary arterioles

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1995.268.6.h2487 ◽

1995 ◽

Vol 268 (6) ◽

pp. H2487-H2494 ◽

Cited By ~ 6

Author(s):

D. V. DeFily ◽

J. L. Patterson ◽

W. M. Chilian

Keyword(s):

Coronary Circulation ◽

Beta Blockade ◽

Adenosine Receptor Antagonist ◽

Endogenous Production ◽

Adenosine Antagonism ◽

Metabolic Stimulation ◽

Metabolic Vasodilation ◽

Baseline Diameter ◽

Made In ◽

Coronary Arterioles

In the coronary circulation alpha-adrenergic constriction competes with metabolic vasodilation. Because adenosine is produced by the working myocardium and metabolic stimulation results in arteriolar dilation, we tested the hypothesis that coronary arteriolar alpha-adrenergic constriction is attenuated by the endogenous production of adenosine. To test this hypothesis, using fluorescence microscopy during stroboscopic epi-illumination of the epicardial microvasculature, we measured the diameter of coronary arterioles in anesthetized open-chest dogs. Measurements were made in the presence of beta-blockade during selective alpha 1- or alpha 2-adrenoceptor activation (phenylephrine or B-HT-933, respectively) before and in the presence of the nonselective adenosine receptor antagonist 8-p-sulfophenyltheophylline (8-pSPT) and expressed as a percent change in microvascular diameter relative to baseline. alpha 1-Activation produced constriction of coronary arterioles under control conditions, which was not augmented after adenosine antagonism (-12 +/- 2 vs. -7 +/- 3%). In contrast, alpha 2-activation did not constrict coronary arterioles under control conditions; however, blockade of adenosine receptors unmasked a significant constriction (0 +/- 2 vs. -7 +/- 2%, P < 0.05). Also adenosine antagonism did not significantly alter the baseline diameter of coronary arterioles. These results demonstrate that endogenously produced adenosine modulates alpha 2-adrenergic constriction of coronary arterioles but not alpha 1-adrenergic constriction, and therefore we speculate that the competition between alpha-adrenergic constriction and metabolic vasodilation is mediated by the alpha 1-adrenoceptor.

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Adenosine antagonism by purines, pteridines and benzopteridines in human fibroblasts

Biochemical Pharmacology ◽

10.1016/0006-2952(81)90062-9 ◽

1981 ◽

Vol 30 (4) ◽

pp. 325-333 ◽

Cited By ~ 111

Author(s):

Robert F. Bruns

Keyword(s):

Human Fibroblasts ◽

Adenosine Antagonism

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Theophylline's inhibition of antigen-induced contraction of human parenchymal strips is independent of adenosine antagonism

European Journal of Pharmacology ◽

10.1016/0014-2999(87)90114-2 ◽

1987 ◽

Vol 142 (2) ◽

pp. 253-260 ◽

Cited By ~ 3

Author(s):

Fiona E. Napier ◽

Diana M. Temple

Keyword(s):

Adenosine Antagonism

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Effect of raised portal venous pressure and postocclusive hyperemia on superior mesenteric arterial resistance in control and adenosine receptor blocked state in cats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y86-219 ◽

1986 ◽

Vol 64 (10) ◽

pp. 1296-1301 ◽

Cited By ~ 2

Author(s):

W. Wayne Lautt

Keyword(s):

Arterial Pressure ◽

Adenosine Receptor ◽

Venous Pressure ◽

Portal Pressure ◽

Systemic Blood Pressure ◽

Portal Venous Pressure ◽

Arterial Perfusion ◽

Resistance Vessels ◽

Adenosine Antagonist ◽

Adenosine Antagonism

Superior mesenteric arterial (SMA) blood flow was measured in pentobarbital-anesthetized cats using a noncannulating electromagnetic flowprobe. The selective adenosine antagonist 8-phenyltheophylline (8-PT) antagonized the dilator effect of infused adenosine but not isoproterenol. The vasodilation in response to reduced arterial perfusion pressure (autoregulation) was blocked by the adenosine receptor blockade, which also reduced the degree of postocclusive (1 min) hyperemia by one-half to two-thirds. The remainder of the hyperemia may have been due partially to adenosine, since exogenous adenosine still produced a small vasodilation (26%), so effects of endogenous adenosine could also still be expected to exert a small effect. Myogenic effects appear unlikely to be the mechanism of the small remaining hyperemia, since venous pressure increments within physiologically relevant ranges did not cause altered SMA conductance, and arterial dilation in response to large decreases in arterial pressure could be blocked by adenosine antagonism. Portal pressure was increased using hepatic nerve stimulation (8 Hz) to raise pressure from 7.0 to 12.4 mmHg (1 mmHg = 133.3 Pa). The small vasoconstriction seen in the SMA was due to the rise in systemic blood pressure, since prevention of a rise in SMA pressure prevented the response and 8-PT blocked the response (previously shown to block arterial pressure–flow autoregulation). An equal rise in PVP imposed by partial occlusion of the portal vein did not lead to changes in SMA vascular conductance. Thus, we conclude that within physiologically relevant ranges of arterial and portal venous pressure, the SMA does not show myogenic responses of the resistance vessels.

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