Role of adenosine in coronary autoregulation

1986 ◽  
Vol 250 (4) ◽  
pp. H558-H566 ◽  
Author(s):  
F. L. Hanley ◽  
M. T. Grattan ◽  
M. B. Stevens ◽  
J. I. Hoffman
Keyword(s):  
Steady State ◽  
Adenosine Deaminase ◽  
Low Pressure ◽  
Catalytic Subunit ◽  
Coronary Resistance ◽  
Pressure Flow ◽  
Intracoronary Infusion ◽  
Adenosine Concentration ◽  
Anesthetized Dogs

The role of cardiac interstitial adenosine as an important metabolite in coronary autoregulation has not been established. We therefore measured steady-state cardiac interstitial adenosine concentration at a high and a low coronary inflow pressure using an epicardial diffusion well in anesthetized dogs. Although coronary resistance for the high and low pressure points showed highly significant differences (P less than 0.001), adenosine averaged 302 +/- 98 and 286 +/- 91 (SD) pmol/ml for the high and low pressure points, respectively (P greater than 0.20). Cardiac interstitial adenosine concentration was then measured with and without an intracoronary infusion of adenosine deaminase catalytic subunit. Adenosine averaged 28 +/- 21 (SD) pmol/ml during the infusion compared with 281 +/- 68 during control conditions (P less than 0.001). Finally, pressure-flow relations were obtained with and without the adenosine deaminase infusion, and there was no loss of autoregulation in the pressure of adenosine deaminase. These findings indicate that intracoronary adenosine deaminase markedly reduces interstitial adenosine concentration, that cardiac interstitial adenosine concentration remains constant during autoregulation, and that the coronary bed autoregulates normally when interstitial adenosine is reduced to levels close to zero. We conclude that cardiac interstitial adenosine concentration is not an important component in coronary autoregulation.

Role of adenosine in postprandial and reactive hyperemia in canine jejunum

1992 ◽  
Vol 263 (4) ◽  
pp. G487-G493 ◽  
Author(s):  
D. R. Sawmiller ◽  
C. C. Chou
Keyword(s):  
Blood Flow ◽  
Oxygen Consumption ◽  
Adenosine Deaminase ◽  
Reactive Hyperemia ◽  
Concentration Difference ◽  
Adenosine Concentration ◽  
Anesthetized Dogs ◽  
Series Of Experiments ◽  
Increased Blood Flow

The role of adenosine in postprandial jejunal hyperemia was investigated by determining the effect of placement of predigested food into the jejunal lumen on blood flow and oxygen consumption before and during intra-arterial infusion of dipyridamole (1.5 microM arterial concn) or adenosine deaminase (9 U/ml arterial concn) in anesthetized dogs. Neither drug significantly altered resting jejunal blood flow and oxygen consumption. Before dipyridamole or deaminase, food placement increased blood flow by 30-36%, 26-42%, and 21-46%, and oxygen consumption by 13-22%, 21-22%, and 26-29%, during 0- to 3-, 4- to 7-, and 8- to 11-min placement periods, respectively. Adenosine deaminase abolished the entire 11-min hyperemia, whereas dipyridamole significantly enhanced the initial 7-min hyperemia (45-49%). Both drugs abolished the initial 7-min food-induced increase in oxygen consumption. Dipyridamole attenuated (14%), whereas deaminase did not alter (28%), the increased oxygen consumption that occurred at 8-11 min. Adenosine deaminase also prevented the food-induced increase in venoarterial adenosine concentration difference. In separate series of experiments, luminal placement of food significantly increased jejunal lymphatic adenosine concentration and release. Also, reactive hyperemia was accompanied by an increase in venous adenosine concentration and release. This study provides further evidence to support the thesis that adenosine plays a role in postprandial and reactive hyperemia in the canine jejunum.

Renal interstitial adenosine metabolism during ischemia in dogs

2001 ◽  
Vol 280 (2) ◽  
pp. F231-F238 ◽  
Author(s):  
Akira Nishiyama ◽  
Shoji Kimura ◽  
Hong He ◽  
Katsuyuki Miura ◽  
Matlubur Rahman ◽  
...  
Keyword(s):  
Adenosine Deaminase ◽  
Adenosine Kinase ◽  
The Other ◽  
Local Inhibition ◽  
Other Hand ◽  
Adenosine Concentration ◽  
Anesthetized Dogs ◽  
Fluorometric Analysis

The present study was conducted to determine the metabolism of renal interstitial adenosine under resting conditions and during ischemia. By using a microdialysis method with HPLC-fluorometric analysis, renal interstitial concentrations of adenosine, inosine, and hypoxanthine were assessed in pentobarbital-anesthetized dogs. Average basal renal interstitial concentrations of adenosine, inosine, and hypoxanthine were 0.18 ± 0.04, 0.31 ± 0.05, and 0.35 ± 0.05 μmol/l, respectively. Local inhibition of adenosine kinase with iodotubercidin (10 μmol/l in perfusate) or inhibition of adenosine deaminase with erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA; 100 μmol/l in perfusate) did not change adenosine concentrations in the nonischemic kidneys (0.18 ± 0.04 and 0.24 ± 0.05 μmol/l, respectively). On the other hand, treatment with iodotubercidin+EHNA significantly increased adenosine concentration (0.52 ± 0.07 μmol/l) with significant decreases in inosine and hypoxanthine levels (0.13 ± 0.03 and 0.19 ± 0.04 μmol/l, respectively). During 30 min of ischemia, adenosine, inosine, and hypoxanthine were significantly increased to 0.76 ± 0.29, 2.14 ± 0.45, and 21.8 ± 4.7 μmol/l, respectively. The treatment with iodotubercidin did not alter ischemia-induced increase in adenosine (0.84 ± 0.18 μmol/l); however, EHNA alone markedly enhanced adenosine accumulation (13.54 ± 2.16 μmol/l), the value of which was not augmented by an addition of iodotubercidin (15.80 ± 1.24 μmol/l). In contrast, ischemia-induced increases in inosine and hypoxanthine were inversely diminished by the treatment with iodotubercidin+EHNA (0.90 ± 0.20 and 9.86 ± 1.96 μmol/l, respectively). These results suggest that both adenosine kinase and adenosine deaminase contribute to the metabolism of renal interstitial adenosine under resting conditions, whereas adenosine produced during ischemia is mainly metabolized by adenosine deaminase and the rephosphorylation of adenosine by adenosine kinase is small.

scholarly journals Activities and some properties of 5′-nucleotidase, adenosine kinase and adenosine deaminase in tissues from vertebrates and invertebrates in relation to the control of the concentration and the physiological role of adenosine

1978 ◽  
Vol 174 (3) ◽  
pp. 965-977 ◽  
Author(s):  
J R S Arch ◽  
E A Newsholme
Keyword(s):  
Adenosine Deaminase ◽  
Physiological Role ◽  
Adenosine Kinase ◽  
British Library ◽  
Adenosine Concentration ◽  
Effects Of Ph ◽  
The Difference ◽  
Low Activity

1. The maximal activities of 5′-nucleotidase, adenosine kinase and adenosine deaminase together with the Km values for their respective substrates were measured in muscle, nervous tissue and liver from a large range of animals to provide information on the mechanism of control of adenosine concentration in the tissues. 2. Detailed evidence that the methods used were optimal for the extraction and assay of these enzymes has been deposited as Supplementary Publication SUP 50088 (16pages) at the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K.,from whom copies can be obtained on the terms indicated in Biochem. J. (1978), 169, 5. This evidence includes the effects of pH and temperature on the activities of the enzymes. 3. In many tissues, the activities of 5′-nucleotidase were considerably higher than the sum of the activities of adenosine kinase and deaminase, which suggests that the activity of the nucleotidase must be markedly inhibited in vivo so that adenosine does not accumulate. In the tissues in which comparison is possible, the Km of the nucleotidase is higher than the AMP content of the tissue, and since some of the latter may be bound within the cell, the low concentration of substrate may, in part, be responsible for a low activity in vivo. 4. In most tissues and animals investigated, the values of the Km of adenosine kinase for adenosine are between one and two orders of magnitude lower than those for the deaminase. It is suggested that 5′-nucleotidase and adenosine kinase are simultaneously active so that a substrate cycle between AMP and adenosine is produced: the difference in Km values between kinase and deaminase indicates that, via the cycle, small changes in activity of kinase or nucleotidase produce large changes in adenosine concentration. 5. The activities of adenosine kinase or deaminase from vertebrate muscles are inversely correlated with the activities of phosphorylase in these muscles. Since the magnitude of the latter activities are indicative of the anaerobic nature of muscles, this negative correlation supports the hypothesis that an important role of adenosine is the regulation of blood flow in the aerobic muscles.

Role of EDRF/NO in parasympathetic coronary vasodilation following carotid chemoreflex activation in conscious dogs

1994 ◽  
Vol 267 (2) ◽  
pp. H605-H613 ◽  
Author(s):  
W. Shen ◽  
M. Ochoa ◽  
X. Xu ◽  
J. Wang ◽  
T. H. Hintze
Keyword(s):  
Vagus Nerve ◽  
Conscious Dogs ◽  
Coronary Resistance ◽  
Vascular Response ◽  
Coronary Vasodilation ◽  
Relaxing Factor ◽  
Anesthetized Dogs ◽  
Endothelium Derived Relaxing Factor ◽  
Stimulation Of

The role of endothelium-derived relaxing factor (EDRF) in parasympathetic coronary vasodilation following carotid chemoreflex activation induced by nicotine in conscious dogs and stimulation of the vagus nerve in anesthetized dogs was studied. Injection of nicotine (11 +/- 4 micrograms) into the carotid artery increased coronary blood flow (CBF) by 126 +/- 16% from 28 +/- 3 ml/min and reduced late diastolic coronary resistance (LDCR) by 43 +/- 4% from 3.58 +/- 0.52 mmHg.ml-1.min, accompanied by a significant increase in mean arterial pressure and a decrease in heart rate (all P < 0.01). Pacing and propranolol did not change the coronary vascular response to chemoreflex activation. There were still increases in CBF by 113 +/- 17% from 29 +/- 3 ml/min and decreases in LDCR by 41 +/- 5% from 3.13 +/- 0.52 mmHg.ml-1.min (all P < 0.01). After infusion of N omega-nitro-L-arginine (L-NNA) (30 mg/kg), the increase in CBF following chemoreflex activation was only 23 +/- 3% from 37 +/- 3 ml/min, and the fall in LDCR was 19 +/- 3% from 3.09 +/- 0.51 mmHg.ml-1.min. Stimulation of the vagus nerve showed a relationship between stimulation frequency and coronary vasodilation that was significantly inhibited by L-NNA. Thus EDRF plays an important role in mediating parasympathetic coronary vasodilation during chemoreflex activation and perhaps during many reflexes that cause vagal cholinergic vasodilation in the heart.

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)

Interstitial adenosine with dipyridamole: effect of adenosine receptor blockade and adenosine deaminase

1992 ◽  
Vol 263 (2) ◽  
pp. H552-H558 ◽  
Author(s):  
T. Wang ◽  
R. M. Mentzer ◽  
D. G. Van Wylen
Keyword(s):  
Adenosine Deaminase ◽  
Adenosine Receptor ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Metabolite Concentration ◽  
Left Ventricular Myocardium ◽  
Receptor Blockade ◽  
Adenosine Uptake ◽  
Adenosine Concentration ◽  
Anesthetized Dogs

Dipyridamole is proposed to increase coronary blood flow (CBF) by inhibition of adenosine uptake into cells, resulting in an increase in interstitial fluid (ISF) adenosine and an adenosine-mediated vasodilation. The purpose of this study was to determine the changes in CBF and ISF adenosine, inosine, and hypoxanthine during dipyridamole infusion in the absence or presence of adenosine receptor blockade or adenosine deaminase. To sample cardiac ISF, cardiac microdialysis probes were implanted in the left ventricular myocardium of chloralose-urethan-anesthetized dogs and perfused with Krebs-Henseleit buffer. The metabolite concentration in the effluent dialysate was used as an index of intramyocardial ISF metabolite concentration. In response to dipyridamole, CBF and dialysate adenosine concentration increased 4.4-fold and 2.2-fold, respectively, whereas dialysate inosine was unchanged and dialysate hypoxanthine decreased 50%. Adenosine receptor blockade, achieved by intracoronary 8-(p-sulfophenyl)theophylline infusion, attenuated the increase in CBF induced by dipyridamole without changing dialysate adenosine concentration. Adenosine deaminase fully attenuated the dipyridamole-induced increases in CBF and dialysate adenosine. These results demonstrate that dipyridamole increases ISF adenosine in the dog and suggest that adenosine is the sole mediator of dipyridamole-induced coronary vasodilation.

Role of adenosine for reactive hyperemia in normal and stunned porcine myocardium

1992 ◽  
Vol 263 (4) ◽  
pp. H1119-H1127 ◽  
Author(s):  
K. A. Kirkeboen ◽  
G. Aksnes ◽  
K. Lande ◽  
A. Ilebekk
Keyword(s):  
Adenosine Deaminase ◽  
Reactive Hyperemia ◽  
Nucleoside Transport ◽  
Normal Myocardium ◽  
Stunned Myocardium ◽  
Segment Length ◽  
Doppler Flowmetry ◽  
Reduced Volume ◽  
Adenosine Concentration

The role of adenosine for reactive hyperemia in normal and stunned myocardium was examined in 16 open-chest barbiturate-anesthetized pigs. Interstitial adenosine concentration was reduced or enhanced by intracoronary infusion of adenosine deaminase or the nucleoside transport inhibitor R 75231, respectively. In normal myocardium, adenosine deaminase reduced volume of hyperemia (Doppler flowmetry) after a 30-s left anterior descending coronary artery (LAD) occlusion by 20% (6-34%; P < 0.05), whereas R 75231 increased volume of hyperemia by 15% (2-24%; P < 0.05). Adenosine deaminase reduced volume of hyperemia after a 2-min LAD occlusion by 27% (13-37%; P < 0.001), whereas R 75231 increased volume of hyperemia by 66% (53-159%; P < 0.001). Adenosine deaminase and R 75231 did not affect maximal hyperemia. Volume of hyperemia after a 2-min LAD occlusion was reduced in stunned myocardium (%systolic segment length shortening reduced by approximately 45%, ultrasonic technique) but not further altered by either adenosine deaminase or R 75231. These findings show that adenosine contributes to reactive hyperemia after 30-120 s of ischemia in normal myocardium and indicate that the reduced reactive hyperemia in stunned myocardium is due to reduced accumulation of adenosine during ischemia.

Adenosine deaminase attenuates canine coronary vasodilation during systemic hypoxia

1986 ◽  
Vol 250 (4) ◽  
pp. H579-H583 ◽  
Author(s):  
G. F. Merrill ◽  
H. F. Downey ◽  
C. E. Jones
Keyword(s):  
Blood Flow ◽  
Oxygen Consumption ◽  
Adenosine Deaminase ◽  
Coronary Vasodilation ◽  
Response Efficacy ◽  
Intracoronary Infusion ◽  
Vasodilatory Response ◽  
Systemic Hypoxia ◽  
Arterial Po2

The hypothesis that adenosine mediates the coronary vasodilatory response to hypoxia was tested by determining if intracoronary infusion of the adenosine degrading enzyme, adenosine deaminase (ADA), would attenuate this response. Efficacy of ADA was also evaluated by examining its effect on the coronary responses to exogenous adenosine and to 20-s myocardial ischemia. Experiments were conducted in 14 anesthetized, open-chest dogs ventilated 3-5 min with 3% O2-5% CO2-92% N2 to induce systemic hypoxia. Under control, pre-ADA conditions, hypoxia (arterial PO2 19 +/- 2 mmHg) caused left anterior descending (LAD) coronary blood flow to increase from 100 +/- 12 to 382 +/- 47 ml X min-1 X 100 g-1 (+282%). After infusion of ADA (5 U X kg-1 X min-1 for 8-10 min) into the LAD, equally severe hypoxia (arterial PO2 18 +/- 3 mmHg) caused a significantly smaller increase in LAD flow, 79 +/- 9 to 234 +/- 41 ml X min-1 X 100 g-1 (+195%). Oxygen consumption in the LAD perfusion field was unchanged by hypoxia before ADA but fell significantly during hypoxia after ADA. ADA also attenuated significantly the coronary vasodilatory response to exogenous adenosine and to 20-s ischemia. The results of this investigation demonstrate a significant role of adenosine in the coronary vasodilatory response to systemic hypoxia.

Role of carotid bodies in control of the neuroendocrine response to exercise

2001 ◽  
Vol 281 (4) ◽  
pp. E742-E748 ◽  
Author(s):  
Yoshiharu Koyama ◽  
Robert H. Coker ◽  
Joshua C. Denny ◽  
D. Brooks Lacy ◽  
Kareem Jabbour ◽  
...  
Keyword(s):  
Steady State ◽  
Glucose Production ◽  
Isotopic Dilution ◽  
Sympathetic Response ◽  
Carotid Bodies ◽  
Anesthetized Dogs ◽  
Arterial Plasma ◽  
Exercise Induced ◽  
Response To Exercise

This study was aimed at assessing the role of carotid body function in neuroendocrine and glucoregulatory responses to exercise. The carotid bodies and associated nerves were removed (CBR, n = 6) or left intact (Sham, n = 6) in anesthetized dogs >16 days before experiments, and infusion and sampling catheters were implanted. Conscious dogs were studied at rest and during 150 min of exercise. Isotopic dilution was used to assess glucose production (Ra) and disappearance (Rd). Arterial glucagon was reduced in CBR compared with Sham at rest (29 ± 3 vs. 47 ± 3 pg/ml). During exercise, glucagon increased more in Sham than in CBR (47 ± 9 vs. 15 ± 2 pg/ml). Cortisol and epinephrine levels were similar in the two groups at rest and during exercise. Basal norepinephrine was similar in CBR and Sham. During exercise, norepinephrine increased by 432 ± 124 pg/ml in Sham, but by only 201 ± 28 pg/ml in CBR. Basal arterial plasma glucose was 108 ± 2 and 105 ± 2 mg/dl in CBR and Sham, respectively. Arterial glucose dropped by 10 ± 3 mg/dl at onset of exercise in CBR ( P < 0.01) but was unchanged in Sham (decrease of 3 ± 2 mg/dl, not significant). Basal glucose kinetics were equal in Sham and CBR. At onset of exercise, Raand Rdwere transiently uncoupled in CBR (i.e., Rd> Ra) but were closely matched in Sham. In steady-state exercise, Raand Rdwere closely matched in both groups. Insulin was equal in the basal period and decreased similarly during exercise. These studies suggest that input from the carotid bodies, or receptors anatomically close to them, 1) is important in control of basal glucagon and the exercise-induced increment in glucagon, 2) is involved in the sympathetic response to exercise, and 3) participates in the non-steady-state coupling of Rato Rd, but 4) is not essential to glucoregulation during sustained exercise.

ATP-sensitive potassium channel is essential to maintain basal coronary vascular tone in vivo

1992 ◽  
Vol 262 (5) ◽  
pp. C1220-C1227 ◽  
Author(s):  
F. F. Samaha ◽  
F. W. Heineman ◽  
C. Ince ◽  
J. Fleming ◽  
R. S. Balaban
Keyword(s):  
Competitive Inhibitor ◽  
K Channel ◽  
Resonance Spectroscopy ◽  
Coronary Resistance ◽  
Tissue Ischemia ◽  
Isolated Hearts ◽  
Anesthetized Dogs ◽  
State Increase

Glibenclamide, a known selective inhibitor of ATP-sensitive potassium channels, was infused into the coronary vasculature of anesthetized dogs and of isolated perfused rabbit hearts to assess the role of this channel in the maintenance of basal coronary resistance. Infusion of glibenclamide at a concentration of 55-80 microM in the dogs resulted in a twofold steady-state increase in coronary resistance with resultant tissue ischemia. Infusion of 1 microM glibenclamide in the isolated hearts resulted in a 67% increase in coronary resistance with resultant tissue ischemia. The ischemic changes were reversible upon removal of the drug. These findings indicate that the ATP-sensitive K+ channel plays a significant role in the maintenance of basal coronary resistance in vivo. Higher concentrations of glibenclamide (80-100 microM) in the in vivo dog heart consistently gave rise to an oscillating pattern of coronary flow. These oscillations were either eliminated or decreased in amplitude and frequency by the infusion of 8-phenyltheophylline, a specific competitive inhibitor of adenosine receptors. 31P-nuclear magnetic resonance spectroscopy performed at the peaks and troughs of these oscillations revealed oscillation of the phosphorylation potential at the same frequency. Thus adenosine release caused by tissue ischemia appears to play a major role in creating the oscillating pattern of coronary blood flow, that occurs during the inhibition of ATP-sensitive K+ channels by glibenclamide.

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