Coronary vasodilation mediated by T cells expressing choline acetyltransferase

2021 ◽  
Vol 321 (5) ◽  
pp. H933-H939
Author(s):  
Adrian H. Chester ◽  
Ann McCormack ◽  
Edmund J. Miller ◽  
Mohamed N. Ahmed ◽  
Magdi H. Yacoub
Keyword(s):  
T Cells ◽  
Blood Flow ◽  
Blood Vessel ◽  
Coronary Blood Flow ◽  
Choline Acetyltransferase ◽  
Vascular Endothelium ◽  
Coronary Circulation ◽  
Direct Interaction ◽  
Coronary Vasodilation ◽  
Ischemic Events

This study shows ChAT-expressing T cells can induce vasodilation of the blood vessel in the coronary circulation and that this effect relies on a direct interaction between T cells and the coronary vascular endothelium. The study establishes a potential immunomodulatory role for T cells in the coronary circulation. The present findings offer an additional possibility that a deficiency of ChAT-expressing T cells could contribute to reduced coronary blood flow and ischemic events in the myocardium.

Alpha 2-adrenoceptor stimulation can augment coronary vasodilation maximally induced by adenosine in dogs

1989 ◽  
Vol 257 (1) ◽  
pp. H132-H140 ◽  
Author(s):  
M. Hori ◽  
M. Kitakaze ◽  
J. Tamai ◽  
K. Iwakura ◽  
A. Kitabatake ◽  
...  
Keyword(s):  
Blood Flow ◽  
Coronary Blood Flow ◽  
Small Dose ◽  
Reactive Hyperemia ◽  
Coronary Perfusion Pressure ◽  
Coronary Perfusion ◽  
Coronary Vasodilation ◽  
Beta Adrenoceptor ◽  
Adenosine Concentration ◽  
Hyperemic Flow

To determine whether alpha 2-adrenoceptor stimulation can augment adenosine-induced coronary vasodilation, 34 open-chest dogs were studied. When a small dose of clonidine (up to 0.24 micrograms.kg-1.min-1 ic) was administered under beta-adrenoceptor blockade, coronary blood flow [312 +/- 16 (SE) ml.100 g-1.min-1] maximally induced by intracoronary infusion of adenosine was further increased (P less than 0.05) by 66 +/- 16 ml.100 g-1.min-1, despite no significant changes in coronary perfusion pressure, myocardial oxygen consumption, and coronary venous adenosine concentration. However, when a larger dose of clonidine (0.36–0.60 micrograms.kg-1.min-1) was infused, adenosine-induced flow progressively decreased. This biphasic action of the alpha 2-adrenoceptor activity was also observed when the dose of norepinephrine was increased during alpha 1-adrenoceptor blockade with prazosin. Norepinephrine up to 0.24 micrograms.kg-1.min-1 (ic) further increased adenosine-induced coronary blood flow by 24 +/- 5% (P less than 0.001), whereas hyperemic flow was decreased by a larger dose of norepinephrine. In contrast to the alpha 2-adrenoceptor stimulation, the alpha 1-adrenoceptor stimulation (norepinephrine with yohimbine) progressively decreased coronary blood flow. Furthermore, with a small dose of clonidine, reactive hyperemic flow significantly increased compared with that without clonidine (303 +/- 13 vs. 355 +/- 13 ml.100 g-1.min-1, P less than 0.001), but a larger dose of clonidine adversely reduced reactive flow (254 +/- 18 ml.100 g-1.min-1, P less than 0.001). Adenosine release during reactive hyperemia with and without intracoronary infusions of clonidine were not altered significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of K ATP + channels and adenosine in regulation of coronary blood flow in the hypertrophied left ventricle

1999 ◽  
Vol 277 (2) ◽  
pp. H617-H625 ◽  
Author(s):  
Peter J. Melchert ◽  
Dirk J. Duncker ◽  
Jay H. Traverse ◽  
Robert J. Bache
Keyword(s):  
Blood Flow ◽  
Left Ventricle ◽  
Coronary Blood Flow ◽  
Coronary Flow ◽  
Rate Pressure Product ◽  
Receptor Blockade ◽  
Channel Activity ◽  
Channel Blockade ◽  
Coronary Vasodilation ◽  
Exercise Induced

In the hypertrophied heart, increased extravascular forces acting to compress the intramural coronary vessels might require augmentation of metabolic vasodilator mechanisms to maintain adequate coronary blood flow. Vascular smooth muscle ATP-sensitive potassium ([Formula: see text]) channel activity is important in metabolic coronary vasodilation, and adenosine contributes to resistance vessel dilation in the hypoperfused heart. Consequently, this study was performed to determine whether[Formula: see text] channels and adenosine have increased importance in exercise-induced coronary vasodilation in the hypertrophied left ventricle. Studies were performed in dogs in which banding of the ascending aorta had resulted in a 66% increase in left ventricular mass in comparison with historic normal animals. Treadmill exercise resulted in increases of coronary blood flow that were linearly related to the increase of heart rate or rate-pressure product. During resting conditions, [Formula: see text]channel blockade with glibenclamide caused a 17 ± 5% decrease in coronary blood flow, similar to that previously observed in normal hearts. Unlike normal hearts, however, glibenclamide blunted the increase in coronary flow that occurred during exercise, causing a significant decrease in the slope of the relationship between coronary flow and the rate-pressure product. Adenosine receptor blockade with 8-phenyltheophylline did not alter coronary blood flow at rest or during exercise. Furthermore, even after[Formula: see text] channel blockade with glibenclamide, the addition of 8-phenyltheophylline had no effect on coronary blood flow. This finding was different from normal hearts, in which the addition of adenosine receptor blockade after glibenclamide impaired exercise-induced coronary vasodilation. The data suggest that, in comparison with normal hearts, hypertrophied hearts have increased reliance on opening of [Formula: see text] channels to augment coronary flow during exercise. Contrary to the initial hypothesis, however, adenosine was not mandatory for exercise-induced coronary vasodilation in the hypertrophied hearts either during control conditions or when [Formula: see text] channel activity was blocked with glibenclamide.

Effects of Cyclic Motion on Coronary Blood Flow

2013 ◽  
Vol 135 (12) ◽  
Author(s):  
Mahmudul Hasan ◽  
David A. Rubenstein ◽  
Wei Yin
Keyword(s):  
Blood Flow ◽  
Shear Stress ◽  
Wall Shear Stress ◽  
Blood Vessel ◽  
Coronary Blood Flow ◽  
Vessel Wall ◽  
Wall Stress ◽  
Blood Vessel Wall ◽  
Flow Parameters ◽  
Cyclic Motion

The goal of this study was to establish a computational fluid dynamics model to investigate the effect of cyclic motion (i.e., bending and stretching) on coronary blood flow. The three-dimensional (3D) geometry of a 50-mm section of the left anterior descending artery (normal or with a 60% stenosis) was constructed based on anatomical studies. To describe the bending motion of the blood vessel wall, arbitrary Lagrangian–Eularian methods were used. To simulate artery bending and blood pressure change induced stretching, the arterial wall was modeled as an anisotropic nonlinear elastic solid using the five-parameter Mooney–Rivlin hyperelastic model. Employing a laminar model, the flow field was solved using the continuity equations and Navier–Stokes equations. Blood was modeled as an incompressible Newtonian fluid. A fluid–structure interaction approach was used to couple the fluid domain and the solid domain iteratively, allowing force and total mesh displacement to be transferred between the two domains. The results demonstrated that even though the bending motion of the coronary artery could significantly affect blood cell trajectory, it had little effect on flow parameters, i.e., blood flow velocity, blood shear stress, and wall shear stress. The shape of the stenosis (asymmetric or symmetric) hardly affected flow parameters either. However, wall normal stresses (axial, circumferential, and radial stress) can be greatly affected by the blood vessel wall motion. The axial wall stress was significantly higher than the circumferential and radial stresses, as well as wall shear stress. Therefore, investigation on effects of wall stress on blood vessel wall cellular functions may help us better understand the mechanism of mechanical stress induced cardiovascular disease.

scholarly journals Functional contribution of P2Y1receptors to the control of coronary blood flow

2011 ◽  
Vol 111 (6) ◽  
pp. 1744-1750 ◽  
Author(s):  
Shawn B. Bender ◽  
Zachary C. Berwick ◽  
M. Harold Laughlin ◽  
Johnathan D. Tune
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Coronary Blood Flow ◽  
Coronary Vasodilation ◽  
Pressure Flow ◽  
Coronary Pressure ◽  
Mrs 2179 ◽  
Dependent Mechanism

Activation of ADP-sensitive P2Y1receptors has been proposed as an integral step in the putative “nucleotide axis” regulating coronary blood flow. However, the specific mechanism(s) and overall contribution of P2Y1receptors to the control of coronary blood flow have not been clearly defined. Using vertically integrative studies in isolated coronary arterioles and open-chest anesthetized dogs, we examined the hypothesis that P2Y1receptors induce coronary vasodilation via an endothelium-dependent mechanism and contribute to coronary pressure-flow autoregulation and/or ischemic coronary vasodilation. Immunohistochemistry revealed P2Y1receptor expression in coronary arteriolar endothelial and vascular smooth muscle cells. The ADP analog 2-methylthio-ADP induced arteriolar dilation in vitro and in vivo that was abolished by the selective P2Y1antagonist MRS-2179 and the nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester. MRS-2179 did not alter baseline coronary flow in vivo but significantly attenuated coronary vasodilation to ATP in vitro and in vivo and the nonhydrolyzable ATP analog ATPγS in vitro. Coronary blood flow responses to alterations in coronary perfusion pressure (40–100 mmHg) or to a brief 15-s coronary artery occlusion were unaffected by MRS-2179. Our data reveal that P2Y1receptors are functionally expressed in the coronary circulation and that activation produces coronary vasodilation via an endothelium/nitric oxide-dependent mechanism. Although these receptors represent a critical component of purinergic coronary vasodilation, our findings indicate that P2Y1receptor activation is not required for coronary pressure-flow autoregulation or reactive 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.

Control of Coronary Blood Flow during Exercise

2002 ◽  
Vol 227 (4) ◽  
pp. 238-250 ◽  
Author(s):  
Johnathan D. Tune ◽  
Keith Neu Richmond ◽  
Mark W. Gorman ◽  
Eric O. Feigl
Keyword(s):  
Blood Flow ◽  
Oxygen Consumption ◽  
Coronary Blood Flow ◽  
Myocardial Oxygen Consumption ◽  
Coronary Vasodilation ◽  
Compensatory Mechanisms ◽  
Feed Forward ◽  
Physiological Conditions ◽  
Coronary Flow Regulation ◽  
Limited Oxygen

Under normal physiological conditions, coronary blood flow is closely matched with the rate of myocardial oxygen consumption. This matching of flow and metabolism is physiologically Important due to the limited oxygen extraction reserve of the heart. Thus, when myocardial oxygen consumption is increased, as during exercise, coronary vasodilation and increased oxygen delivery are critical to preventing myocardial underperfusion and Ischemia. Exercise coronary vasodilation is thought to be mediated primarily by the production of local metabolic vasodilators released from cardiomyocytes secondary to an increase in myocardial oxygen consumption. However, despite various investigations into this mechanism, the medlator(s) of metabolic coronary vasodilation remain unknown. As will be seen in this review, the adenosine, K+ATP channel and nitric oxide hypotheses have been found to be inadequate, either alone or in combination as multiple redundant compensatory mechanisms. Prostaglandins and potassium are also not important in steady-state coronary flow regulation. Other factors such as ATP and endothelium-derived hyperpolarizing factors have been proposed as potential local metabolic factors, but have not been examined during exercise coronary vasodilation. In contrast, norepinephrine released from sympathetic nerve endings mediates a feed-forward ß-adrenoceptor coronary vasodilation that accounts for -25% of coronary vasodilation observed during exercise. There is also a feed-forward α-adrenoceptor-mediated vasoconstriction that helps maintain blood flow to the vulnerable subendocardium when heart rate, myocardial contractility, and oxygen consumption are elevated during exercise. Control of coronary blood flow during pathophysiological conditions such as hypertension, diabetes mellitus, and heart failure is also addressed.

scholarly journals Obesity decreases the contribution of Kv channels to hypoxic coronary vasodilation

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Hannah E. Clark ◽  
Hana E. Baker ◽  
Adam G. Goodwill ◽  
Bianca S. Blaettner ◽  
Michael C. Kozlowski ◽  
...  
Keyword(s):  
Blood Flow ◽  
Coronary Blood Flow ◽  
Coronary Flow ◽  
Functional Expression ◽  
K Channel ◽  
Coronary Vasodilation ◽  
Kv Channels ◽  
Arterial Blood ◽  
Before And After ◽  
Arterial Po2

Background and Hypothesis: Our group previously demonstrated that reductions in the functional expression of voltage-dependent K+ (Kv) channels contribute to impaired metabolic control of coronary blood flow in the setting of obesity. This study tested the hypothesis that obesity diminishes the contribution of Kv channels to coronary vasodilation in response to hypoxemia. Experimental Design or Project Methods: Control lean (n = 7) and obese (n = 5) swine were anesthetized and the heart exposed via left lateral thoracotomy. Coronary blood flow was measured in response to hypoxemia, before and after inhibition of Kv channels by 4-aminopyridine (4-AP; 0.3 mg/kg, iv), by a flow probe placed about the left anterior descending coronary artery. Hypoxemia was induced by progressive increases in the amount of nitrogen introduced into the ventilator. Arterial blood samples were obtained at each reduction in arterial oxygenation via a catheter placed in the femoral artery. Results: Blood pressure decreased from ~88 ± 5 mmHg to ~68 ± 6 mmHg (P = 0.01) as arterial PO2 was reduced below 50 mmHg in both lean and obese swine (P = 0.51). In lean swine, coronary flow progressively increased from ~0.6 to >3.0 ml/min/g as arterial PO2 was reduced. This response was decreased by ~40% in obese swine and by ~30% in lean swine treated with 4-AP. Administration of 4AP had no effect on coronary flow in obese swine. Conclusion and Potential Impact: These data support that Kv channels contribute to increases in coronary flow in response to hypoxemia in lean swine and that reductions in Kv channel function contribute to impaired hypoxic coronary vasodilation in obese swine. We propose that therapeutic targeting of obesity associated pathways (angiotensin-aldosterone system) known to influence K+ channel expression could improve coronary microvascular function and cardiovascular outcomes in subjects with obesity. Supported by R01 HL136386; T35 HL 110854.

Endothelium-Derived Hyperpolarizing Factor—Fact or Fiction?

Physiology ◽  
2000 ◽  
Vol 15 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Markus Hecker
Keyword(s):  
Blood Flow ◽  
Arachidonic Acid ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Vascular Endothelium ◽  
Crucial Role ◽  
Coronary Circulation ◽  
Diffusible Factor

The vascular endothelium releases a diffusible factor that hyperpolarizes and hence relaxes vascular smooth muscle cells predominantly through activation of Ca2+-dependent K+ channels. In the coronary circulation, this endothelium-derived hyperpolarizing factor appears to be a cytochrome P450-derived arachidonic acid epoxide, the release of which may play a crucial role in the maintenance of coronary blood flow in arteriosclerosis.

Nitric oxide modulates right ventricular flow and oxygen consumption during norepinephrine infusion

2002 ◽  
Vol 282 (2) ◽  
pp. H696-H703 ◽  
Author(s):  
Srinath Setty ◽  
Johnathan D. Tune ◽  
H. Fred Downey
Keyword(s):  
Nitric Oxide ◽  
Heart Rate ◽  
Blood Flow ◽  
Oxygen Consumption ◽  
Right Ventricular ◽  
Ventricular Function ◽  
Coronary Blood Flow ◽  
Right Ventricular Function ◽  
Utilization Efficiency ◽  
Coronary Vasodilation

This study was designed to test if nitric oxide (NO) contributes to norepinephrine-induced right coronary vasodilation and if NO blunts the norepinephrine-induced increase in myocardial oxygen consumption (MV˙o 2) in the right ventricle. In five anesthetized, open-chest dogs, mean aortic pressure, heart rate, right ventricular rate of pressure development over time (dP/d t), right coronary blood flow, and right ventricular MV˙o 2 were measured before and during graded intracoronary infusions of norepinephrine in the absence and presence of a NO synthase blocker, N ω-nitro-l-arginine methyl ester (l-NAME; 150 μg/min ic). During both conditions, right coronary blood flow and right ventricular MV˙o 2 significantly increased with graded infusions of norepinephrine. l-NAME significantly blunted the coronary hyperemic response to norepinephrine, althoughl-NAME did not alter the relationship between right ventricular MV˙o 2 and norepinephrine dose. However, when right ventricular function was indexed by heart rate × right ventricular maximum dP/d t × peak right ventricular systolic pressure, l-NAME significantly increased the oxygen cost of right ventricular function. These results indicate that NO contributes to norepinephrine-induced right coronary vasodilation and improves right ventricular oxygen utilization efficiency.

Estimation of intramyocardial pressure and coronary blood flow distribution

1988 ◽  
Vol 255 (3) ◽  
pp. H664-H672 ◽  
Author(s):  
Y. Sun ◽  
H. Gewirtz
Keyword(s):  
Blood Flow ◽  
Coronary Blood Flow ◽  
Coronary Circulation ◽  
Regression Line ◽  
Flow Distribution ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Blood Flow Distribution ◽  
Intramyocardial Pressure ◽  
D Model

To characterize the intramyocardial pressure (IMP) and coronary blood flow distribution in a stenosed coronary circulation, we compared four analog circuits for modeling coronary impedance. The resistor (R)-diode (D) model simulates vascular collapse, and the capacitor (C) simulates compliance effect. Identification of the best model and magnitudes of the endocardial and epicardial IMPs (IMPendo and IMPepi) was done retrospectively using data from studies in 28 anesthetized swine. Performance evaluation was based on comparison of model predicted vs. observed coronary distal pressure (DP) waveforms and endocardial-to-epicardial (endo-epi) flow ratios as determined by radiolabeled microspheres. The R-D-C model gave the best performance at IMPendo = 1.1 times left ventricular pressure (LVP), and IMPepi = 0.1.LVP + 15 mmHg; with good fit to DP (r = 0.98, slope of regression line = 1.0) and estimates of endo-epi flow ratio (r = 0.78, slope = 1.01, P less than 0.02, SEE = 0.21, n = 139). The R-D model gave comparable results even though capacitance was omitted. Although R-C and R models predicted distal coronary pressure well, they failed to predict endo-epi flow ratios (r less than 0.50). The R-D-C and R-D models were applied in seven prospective studies. Both models generated reasonable estimates of endo-epi flow distribution (r = 0.78, n = 50). Thus the R-D-C or R-D models of the stenosed coronary circulation can be used to provide reliable estimates of transmural blood flow distribution.

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