Adenosine is not responsible for local metabolic control of coronary blood flow in dogs during exercise

2000 ◽  
Vol 278 (1) ◽  
pp. H74-H84 ◽  
Author(s):  
Johnathan D. Tune ◽  
Keith Neu Richmond ◽  
Mark W. Gorman ◽  
Ray A. Olsson ◽  
Eric O. Feigl
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Oxygen Consumption ◽  
Metabolic Control ◽  
Coronary Blood Flow ◽  
Myocardial Oxygen Consumption ◽  
Aortic Pressure ◽  
Receptor Blockade ◽  
Adenosine Concentration ◽  
Venous Plasma

The purpose of this investigation was to quantitatively evaluate the role of adenosine in coronary exercise hyperemia. Dogs ( n = 10) were chronically instrumented with catheters in the aorta and coronary sinus, and a flow probe on the circumflex coronary artery. Cardiac interstitial adenosine concentration was estimated from arterial and coronary venous plasma concentrations using a previously tested mathematical model. Coronary blood flow, myocardial oxygen consumption, heart rate, and aortic pressure were measured at rest and during graded treadmill exercise with and without adenosine receptor blockade with either 8-phenyltheophylline (8-PT) or 8- p-sulfophenyltheophylline (8-PST). In control vehicle dogs, exercise increased myocardial oxygen consumption 4.2-fold, coronary blood flow 3.8-fold, and heart rate 2.5-fold, whereas mean aortic pressure was unchanged. Coronary venous plasma adenosine concentration was little changed with exercise, and the estimated interstitial adenosine concentration remained well below the threshold for coronary vasodilation. Adenosine receptor blockade did not significantly alter myocardial oxygen consumption or coronary blood flow at rest or during exercise. Coronary venous and estimated interstitial adenosine concentration did not increase to overcome the receptor blockade with either 8-PT or 8-PST as would be predicted if adenosine were part of a high-gain, negative-feedback, local metabolic control mechanism. These results demonstrate that adenosine is not responsible for local metabolic control of coronary blood flow in dogs during exercise.

Role of adenosine in norepinephrine-induced coronary vasodilation

1997 ◽  
Vol 273 (2) ◽  
pp. H557-H565 ◽  
Author(s):  
R. Van Bibber ◽  
D. W. Stepp ◽  
K. Kroll ◽  
E. O. Feigl
Keyword(s):  
Blood Flow ◽  
Oxygen Consumption ◽  
Coronary Blood Flow ◽  
Adenosine Receptor ◽  
Myocardial Oxygen Consumption ◽  
Temporal Correlation ◽  
Distributed Model ◽  
Receptor Blockade ◽  
Adenosine Concentration

Adenosine has been postulated to be the physiological transmitter coupling increases in coronary blood flow to increases in myocardial metabolism. The purpose of this experiment was to evaluate the role of adenosine in the coronary hyperemia due to norepinephrine. In 11 anesthetized, closed-chest canine preparations, the left main coronary artery was cannulated and perfused with blood at 100 mmHg. Coronary blood flow and myocardial oxygen consumption were measured, and interstitial adenosine concentration was estimated from arterial and coronary venous measurements using a distributed model. Adenosine receptor blockade with 8-phenyltheophylline (8-PT) was used to shift the adenosine dose-response curve 12-fold. During intracoronary norepinephrine infusion, coronary blood flow and myocardial oxygen consumption increased similarly before and after 8-PT, demonstrating a lack of an effect from the adenosine receptor blockade. Before 8-PT, estimated interstitial adenosine increased to a vasoactive concentration (220 nM); however, the temporal correlation with coronary blood flow was poor. After 8-PT, a similar increase in estimated interstitial adenosine was found, demonstrating that there was no augmentation in adenosine concentration to overcome the adenosine receptor blockade. Thus adenosine could not be responsible for the increase in coronary blood flow after adenosine receptor blockade and therefore is not required for norepinephrine-induced hyperemia.

Role of adenosine in local metabolic coronary vasodilation

1999 ◽  
Vol 276 (5) ◽  
pp. H1425-H1433 ◽  
Author(s):  
Toyotaka Yada ◽  
Keith Neu Richmond ◽  
Richard van Bibber ◽  
Keith Kroll ◽  
Eric O. Feigl
Keyword(s):  
Blood Flow ◽  
Oxygen Consumption ◽  
Coronary Blood Flow ◽  
Adenosine Receptor ◽  
Myocardial Oxygen Consumption ◽  
Receptor Blockade ◽  
Coronary Vasodilation ◽  
Paired Pulse ◽  
Adenosine Concentration

Adenosine has been postulated to mediate the increase in coronary blood flow when myocardial oxygen consumption is increased. The aim of this study was to evaluate the role of adenosine when myocardial oxygen consumption was augmented by cardiac paired-pulse stimulation without the use of catecholamines. In 10 anesthetized closed-chest dogs, coronary blood flow was measured in the left circumflex coronary artery, and myocardial oxygen consumption was calculated using the arteriovenous oxygen difference. Cardiac interstitial adenosine concentration was estimated from coronary venous and arterial plasma adenosine measurements using a previously described multicompartmental, axially distributed mathematical model. Paired stimulation increased heart rate from 55 to 120 beats/min, increased myocardial oxygen consumption 104%, and increased coronary blood flow 92%, but the estimated interstitial adenosine concentration remained below the threshold for coronary vasodilation. After adenosine-receptor blockade with 8-phenyltheophylline (8-PT), coronary blood flow and myocardial oxygen consumption were not significantly different from control values. Paired-pulse pacing during adenosine-receptor blockade resulted in increases in myocardial oxygen consumption and coronary blood flow similar to the response before 8-PT. Coronary venous and estimated interstitial adenosine concentration did not increase to overcome the adenosine blockade by 8-PT. These results demonstrate that adenosine is not required for the local metabolic control of coronary blood flow during pacing-induced increases in myocardial oxygen consumption.

Alteration in myocardial oxygen balance during exercise after beta-adrenergic blockade in dogs

1980 ◽  
Vol 49 (1) ◽  
pp. 28-33 ◽  
Author(s):  
G. R. Heyndrickx ◽  
J. L. Pannier ◽  
P. Muylaert ◽  
C. Mabilde ◽  
I. Leusen
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Oxygen Consumption ◽  
Myocardial Blood Flow ◽  
Coronary Blood Flow ◽  
Coronary Sinus ◽  
Myocardial Oxygen Consumption ◽  
Left Ventricular ◽  
Adrenergic Blockade ◽  
Oxygen Balance

The effects of beta-adrenergic blockade upon myocardial blood flow and oxygen balance during exercise were evaluated in eight conscious dogs, instrumented for chronic measurements of coronary blood flow, left ventricular pressure, aortic blood pressure, heart rate, and sampling of arterial and coronary sinus venous blood. The administration of propranolol (1.5 mg/kg iv) produced a decrease in heart rate, peak left ventricular (LV) dP/dt, LV (dP/dt/P, and an increase in LV end-diastolic pressure during exercise. Mean coronary blood flow and myocardial oxygen consumption were lower after propranolol than at the same exercise intensity in control conditions. The oxygen delivery-to-oxygen consumption ratio and the coronary sinus oxygen content were also significantly lower. It is concluded that the relationship between myocardial oxygen supply and demand is modified during exercise after propranolol, so that a given level of myocardial oxygen consumption is achieved with a proportionally lower myocardial blood flow and a higher oxygen extraction.

Neuropeptide Y and coronary vasoconstriction: role of thromboxane A2

1992 ◽  
Vol 263 (4) ◽  
pp. H1045-H1053
Author(s):  
S. E. Martin ◽  
J. T. Kuvin ◽  
S. Offenbacher ◽  
B. M. Odle ◽  
R. E. Patterson
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Oxygen Consumption ◽  
Neuropeptide Y ◽  
Coronary Blood Flow ◽  
Myocardial Oxygen Consumption ◽  
Thromboxane A2 ◽  
Coronary Resistance ◽  
Txa2 Receptor

We previously reported that coronary constriction following neuropeptide Y (NPY) was alleviated by cyclooxygenase blockade. To determine the role of thromboxane A2 (TxA2), anesthetized dogs received two paired doses of NPY given 2 h apart. Nine control dogs received NPY alone. Nine test dogs received one of three TxA2 receptor antagonists given between the doses of NPY. Also, five dogs received NPY during which prostaglandins were measured. In controls, NPY decreased coronary blood flow and increased aortic pressure; coronary resistance was increased significantly. Heart rate fell, and myocardial oxygen consumption was unchanged. Thromboxane receptor blockers significantly relieved the coronary constrictor effect of NPY. The reduction in coronary blood flow was blunted, while heart rate, first derivative of left ventricular pressure, and myocardial oxygen consumption were unchanged. Alleviation by TxA2 receptor blockade paralleled that reported for cyclooxygenase inhibitors. Also, significant increases in coronary venous TxA2 were seen at the time of maximal increases in coronary resistance, while prostacyclin was unchanged. In summary, TxA2 appears to mediate part of the coronary constrictor effect of NPY.

Left ventricular heat production during induced tachycardia in the intact dog

1965 ◽  
Vol 209 (1) ◽  
pp. 33-36 ◽  
Author(s):  
Skoda Afonso ◽  
David H. McKenna ◽  
George S. O'Brien ◽  
George G. Rowe ◽  
Charles W. Crumpton
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Oxygen Consumption ◽  
Metabolic Rate ◽  
Coronary Blood Flow ◽  
Heat Production ◽  
Myocardial Oxygen Consumption ◽  
Left Ventricular ◽  
Metabolic Parameters ◽  
Heat Control

It is well established that heart rate is a determinant of myocardial oxygen consumption. However, it has not been demonstrated that the increase of oxygen consumption at faster rates actually represents loss of energy, degraded as heat. Control measurements of systemic and coronary hemodynamic and metabolic parameters and left ventricular heat production (measured by a recently reported method) were obtained in 10 dogs. Tachycardia was then induced electrically and the same parameters redetermined. Significant increases occurred in coronary blood flow, cardiac metabolic rate of oxygen, and left ventricular heat production. The elevated myocardial oxygen consumption at higher rates is associated with increased heat production.

Endogenous nitric oxide modulates myocardial oxygen consumption in canine right ventricle

2001 ◽  
Vol 281 (2) ◽  
pp. H831-H837 ◽  
Author(s):  
Srinath Setty ◽  
Xiaoming Bian ◽  
Johnathan D. Tune ◽  
H. Fred Downey
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Oxygen Consumption ◽  
Right Ventricular ◽  
Coronary Blood Flow ◽  
Myocardial Oxygen Consumption ◽  
Aortic Pressure ◽  
Coronary Perfusion ◽  
Endogenous Nitric Oxide ◽  
The Right

The role of endogenous nitric oxide (NO) in modulating myocardial oxygen consumption (MV˙o 2) is unclear, in part because of systemic and coronary hemodynamic effects of blocking NO release. This study evaluated the effect of NO on right ventricular MV˙o 2 under controlled hemodynamic conditions. In 12 open-chest dogs, N ω-nitro-l-arginine methyl ester (l-NAME, 150 μg/min), a NO synthase (NOS) blocker, was infused into the right coronary artery. Heart rate and mean aortic pressure were constant. Right coronary blood flow and right ventricular MV˙o 2 were measured at normal and elevated right coronary perfusion pressures (RCP) before and afterl-NAME. To avoid effects of NO synthesis blockade on right coronary blood flow, which might have altered right ventricular MV˙o 2, experiments, were conducted during adenosine-induced maximal coronary vasodilation. l-NAME did not affect right coronary blood flow ( P = 0.51). However,l-NAME significantly increased right ventricular MV˙o 2 (6% at RCP 100 mmHg, and 21% at RCP 180 mmHg). Right coronary blood flow varied with perfusion pressure ( P < 0.02), and the elevation of MV˙o 2 produced by l-NAME increased at higher flows ( P < 0.04), consistent with the greater shear stress-mediated release of NO. These findings indicate that endogenous NO limits right ventricular MV˙o 2.

Coronary arteriolar vasoconstriction to angiotensin II is augmented in prediabetic metabolic syndrome via activation of AT1 receptors

2005 ◽  
Vol 288 (5) ◽  
pp. H2154-H2162 ◽  
Author(s):  
Cuihua Zhang ◽  
Jarrod D. Knudson ◽  
Srinath Setty ◽  
Alberto Araiza ◽  
Ü. Deniz Dincer ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Blood Flow ◽  
Oxygen Consumption ◽  
Coronary Blood Flow ◽  
Normal Control ◽  
Myocardial Oxygen Consumption ◽  
Receptor Protein ◽  
Receptor Blockade ◽  
Ang Ii ◽  
High Fat

The metabolic syndrome is associated with activation of the renin-angiotensin system. However, whether the coronary vascular response to ANG II is altered under this condition is unknown. Experiments were conducted in control and chronically high-fat-fed dogs with the prediabetic metabolic syndrome both in vitro (isolated coronary arterioles, 60–110 μm) and in vivo (anesthetized and conscious). We found that plasma renin activity and ANG II levels are elevated in high-fat-fed dogs and that this increase in ANG II is associated with a significant increase in ANG II-mediated coronary vasoconstriction in isolated coronary arterioles and in anesthetized open-chest dogs. The vasoconstriction to ANG II is abolished by ANG II type 1 (AT1) receptor blockade. In conscious chronically instrumented dogs, AT1 receptor blockade with telmisartan improved the balance between coronary blood flow and myocardial oxygen consumption in the high-fat-fed dogs but not in normal control dogs, i.e., the relationship between coronary venous Po2 and myocardial oxygen consumption was shifted upward, toward normal control values. Quantitative assessment of coronary arteriolar AT1 and ANG II type 2 (AT2) receptor mRNA levels by real-time PCR revealed no significant difference between normal control and high-fat-fed dogs; however, Western blot analysis showed a significant increase in AT1 receptor protein level with no change in AT2 receptor protein density. These findings indicate that AT1 receptor-mediated coronary constriction is augmented in the prediabetic metabolic syndrome and contributes to impaired control of coronary blood flow via increases in circulating ANG II and/or coronary arteriolar AT1 receptor density.

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