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

1995 ◽  
Vol 268 (6) ◽  
pp. H2487-H2494 ◽  
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.

The Coronary Circulation

1993 ◽  
Vol 115 (4B) ◽  
pp. 558-561 ◽  
Author(s):  
Robert E. Mates
Keyword(s):  
Bypass Surgery ◽  
Coronary Circulation ◽  
Surgical Techniques ◽  
Diagnostic Techniques ◽  
Resonance Imaging ◽  
Complete Understanding ◽  
Geometric Information ◽  
Artery Disease ◽  
And Control ◽  
Made In

Dramatic advances have been made in the last two decades in the diagnosis and treatment of coronary artery disease. The development of open heart surgical techniques for bypassing occluded arteries made quantitative diagnostic techniques more important. Computer enhanced angiographic methods, together with measurements using tomography, ultrasound and magnetic resonance imaging have greatly improved the precision of the diagnosis. A more complete understanding of coronary mechanics and control has enabled physicians to better interpret the significance of geometric information and to supplement this information with functional assessment of stenosed arteries. Finally, traditional bypass surgery is now supplemented with closed-chest techniques such as balloon angioplasty. Biomedical engineers have been involved in all of these developments. This paper will review these developments and attempt to identify remaining questions.

Role of pertussis toxin-sensitive G protein in metabolic vasodilation of coronary microcirculation

2000 ◽  
Vol 279 (4) ◽  
pp. H1819-H1829 ◽  
Author(s):  
Toshinori Tanikawa ◽  
Hiroshi Kanatsuka ◽  
Ryohji Koshida ◽  
Mitsuaki Tanaka ◽  
Akihiko Sugimura ◽  
...  
Keyword(s):  
G Protein ◽  
Pertussis Toxin ◽  
Atrial Pacing ◽  
Metabolic Demand ◽  
Before And After ◽  
Vehicle Treatment ◽  
Rapid Pacing ◽  
Metabolic Stimulation ◽  
Metabolic Vasodilation

We have previously demonstrated that pertussis toxin (PTX)-sensitive G protein (GPTX) plays a major role in coronary microvascular vasomotion during hypoperfusion. We aimed to elucidate the role of GPTX during increasing metabolic demand. In 18 mongrel dogs, coronary arteriolar diameters were measured by fluorescence microangiography using a floating objective. Myocardial oxygen consumption (MV˙o 2) was increased by rapid left atrial pacing. In six dogs, PTX (300 ng/ml) was superfused onto the heart surface for 2 h to locally block GPTX. In eight dogs, the vehicle (Krebs solution) was superfused in the same way. Before and after each treatment, the diameters were measured during control (130 beats/min) and rapid pacing (260 beats/min) in each group. Metabolic stimulation before and after the vehicle treatment caused 8.6 ± 1.8 and 16.1 ± 3.6% dilation of coronary arterioles <100 μm in diameter (57 ± 8 μm at control, n = 10), respectively. PTX treatment clearly abolished the dilation of arterioles (12.8 ± 2.5% before and 0.9 ± 1.6% after the treatment, P < 0.001 vs. vehicle; 66 ± 8 μm at control, n = 11) in response to metabolic stimulation. The increases in MV˙o 2 and coronary flow velocity were comparable between the vehicle and PTX groups. In four dogs, 8-phenyltheophylline (10 μM, superfusion for 30 min) did not affect the metabolic dilation of arterioles (15.3 ± 2.0% before and 16.4 ± 3.8% after treatment; 84.3 ± 11.0 μm at control, n = 8). Thus we conclude that GPTXplays a major role in regulating the coronary microvascular tone during active hyperemia, and adenosine does not contribute to metabolic vasodilation via GPTX activation.

ATP-sensitive K+ channels and metabolic vasodilation in coronary circulation

1994 ◽  
Vol 1 ◽  
pp. 303
Author(s):  
Kensuke Egashira ◽  
Yousuke Katsuda ◽  
Akira Takeshita
Keyword(s):  
Coronary Circulation ◽  
K Channels ◽  
Metabolic Vasodilation

Adenosine's role in regulating basal coronary arteriolar tone

1986 ◽  
Vol 250 (6) ◽  
pp. H1030-H1036 ◽  
Author(s):  
H. Gewirtz ◽  
R. A. Olsson ◽  
D. L. Brautigan ◽  
P. R. Brown ◽  
A. S. Most
Keyword(s):  
Coronary Circulation ◽  
Relative Reduction ◽  
Atrial Pacing ◽  
Regional Flow ◽  
Intracoronary Infusion ◽  
Adenosine Concentration ◽  
Transmural Flow ◽  
Arteriolar Tone ◽  
Made In

This study examined the role of adenosine in regulating coronary arteriolar tone under basal conditions in the normal coronary circulation. Measurements of hemodynamics and flow (microspheres) were made in eight closed-chest, sedated pigs at 1) control and 2) after 10 min of infusion of adenosine deaminase (ADA, 10 U X kg-1 X min-1) into the left anterior descending (LAD) coronary artery. Heart rate was held constant by atrial pacing. Transmural flow in the distal LAD zone did not change versus control (1.81 +/- 0.36) with ADA (1.78 +/- 0.46). However, in comparison with control the distal LAD:circumflex zone transmural flow ratio (0.96 +/- 0.04) declined (P less than 0.01) during ADA infusion (0.93 +/- 0.04). Similarly, the distal LAD:circumflex zone transmural flow resistance ratio increased significantly (P less than 0.01) versus control (1.04 +/- 0.05) in response to intracoronary ADA infusion (1.08 +/- 0.04). Regional myocardial oxygen consumption in the distal LAD zone did not change versus control (16.9 +/- 3.3 3.3 ml X min-1 X 100 g-1) during ADA (16.9 +/- 4.5). Additional studies in 15 open-chest swine given intracoronary infusion of ADA demonstrated that 1) the enzyme penetrates the interstitial fluid (ISF) and 2) attains ISF levels which are adequate to reduce basal adenosine concentration 10 fold even if substantial increase in adenosine production occurs in response to ADA. Thus, since destruction of adenosine by ADA caused only very modest relative reduction in regional flow, it is likely that the nucleoside plays only a limited role in regulation of arteriolar tone under basal conditions in the normal coronary circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Contribution of adenosine to changes in coronary flow in metabolically stimulated rat heart

1988 ◽  
Vol 66 (2) ◽  
pp. 171-173 ◽  
Author(s):  
John Headrick ◽  
Roger J. Willis
Keyword(s):  
Adenosine Deaminase ◽  
Rat Heart ◽  
Coronary Flow ◽  
Left Ventricular ◽  
Extracellular Adenosine ◽  
Mediated Action ◽  
Adenosine Receptor Antagonist ◽  
Rat Hearts ◽  
Developed Pressure ◽  
Metabolic Stimulation

The extent to which endogenous, extracellular adenosine mediates increased coronary flow in crystalloid-perfused, isovolumic rat hearts stimulated with either norepinephrine or isoproterenol was examined. When infused into the coronary circulation, norepinephrine (1 × 10−7 M) rapidly increased left ventricular developed pressure (LVDP) from 81 ± 6 to 235 ± 13 mmHg (1 mmHg = 133.3 Pa) and coronary flow from 12.7 ± 0.8 to 18.4 ± 0.7 mL∙mn−1∙g−1. The presence of either adenosine deaminase (2 U∙mL−1) or the adenosine receptor antagonist, 8-phenyltheophylline (5 × 10−6 M) in the perfusate of norepinephrine-stimulated hearts augmented the increase in LVDP and ±dP/dtmax by 10–20% but reduced the increase in coronary flow by 34%. Doubling the rate of adenosine deaminase infusion, or infusing the enzyme and 8-phenyltheophylline together did not alter their inhibitory effectiveness. Similar results were observed with hearts stimulated with isoproterenol (5 × 10−8 M). These data show that about a third of the vasodilation that results from the metabolic stimulation of rat heart by catecholamines is due to the receptor-mediated action of extracellular adenosine.

scholarly journals Insulin Sensitivity Assessed by Stable Isotopes with Oral Glucose Administration: Validation with Euglycaemic Clamp

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Leslie Bluck ◽  
Rachel Williams ◽  
Sarah Jackson ◽  
Burak Salgin ◽  
Carlo Acerini ◽  
...  
Keyword(s):  
Stable Isotopes ◽  
Insulin Sensitivity ◽  
Oral Dose ◽  
Glucose Uptake ◽  
Intravenous Administration ◽  
Oral Glucose ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Euglycaemic Clamp ◽  
Endogenous Production ◽  
Made In

Methods of determining insulin sensitivity that use an oral challenge of glucose are preferred to those using intravenous administration since the measurement is made in conditions more akin to normal physiology. One previously reported protocol (ODILE) studies glucose uptake in isolation from absorption and endogenous production by the intravenous administration of tracer approximately forty-five minutes after the oral dose is given. However, this methodology has not been validated against other accredited procedures. This study utilizes the euglycemic hyperinsulinemic clamp in order to validate the ODILE method.

Beta blockade and coronary circulation

1976 ◽  
Vol 91 (4) ◽  
pp. 536-537 ◽  
Author(s):  
M.H. Frick ◽  
K.S. Virtanen
Keyword(s):  
Coronary Circulation ◽  
Beta Blockade

Nitric oxide and H2O2 contribute to reactive dilation of isolated coronary arterioles

2004 ◽  
Vol 287 (6) ◽  
pp. H2461-H2467 ◽  
Author(s):  
Akos Koller ◽  
Zsolt Bagi
Keyword(s):  
Coronary Circulation ◽  
Reactive Hyperemia ◽  
No Synthase ◽  
Intraluminal Pressure ◽  
Metabolic Factors ◽  
Hemodynamic Forces ◽  
Vasoactive Factors ◽  
Induced Changes ◽  
Coronary Arterioles

The role of metabolic factors derived from cardiac muscle in the development of reactive hyperemia after brief occlusions of the coronary circulation seems to be well established. However, the contribution of occlusion-induced changes in hemodynamic forces to eliciting reactive hyperemia is less known. We hypothesized that in isolated coronary arterioles changes in intraluminal pressure and flow, during and after release of occlusion (O/R), themselves via activating intrinsic mechanosensitive mechanisms, elicit release of vasoactive factors resulting in reactive dilations. Thus in isolated coronary arterioles (diameter: 88 ± 8 μm) changes in diameter to changes in pressure or pressure plus flow (P+F) during and after a brief period (30, 60, and 120 s) of O/R of cannulating tube were measured by videomicroscopy. In response to both types of O/R, diameter first decreased, then, subsequently increased during occlusions. When only pressure was changed (from 80-10-80 mmHg), after release of occlusion, peak dilations increased as a function of the duration of occlusions. After flow was established (30 μl/min), O/R elicited changes in both pressure and flow (from 80-10-80 mmHg and from 0 to 30 μl/min). In these conditions, after the release of occlusions, not only the peak but also the duration of reactive dilation increased significantly as a function of the length of occlusions. The dilations during, and peak dilations after occlusions both in pressure and P+F protocols were significantly reduced by the inhibition of NO synthase with Nω-nitro-l-arginine-methyl-ester (l-NAME) or by endothelium removal, whereas duration of postocclusion dilations were reduced by l-NAME or by endothelium removal only in P+F protocols. Furthermore, in both protocols, catalase significantly reduced the peak but not the duration of reactive dilations. Thus, mechanosensitive mechanisms that are sensitive to deformation, pressure, stretch, and wall shear stress elicit release of NO and H2O2, resulting in reactive dilation of isolated coronary arterioles.

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