Exercise training restores adenosine-induced relaxation in coronary arteries distal to chronic occlusion

2000 ◽  
Vol 278 (6) ◽  
pp. H1984-H1992 ◽  
Author(s):  
Cristine L. Heaps ◽  
Michael Sturek ◽  
Julie A. Rapps ◽  
M. Harold Laughlin ◽  
Janet L. Parker
Keyword(s):  
Coronary Artery ◽  
Exercise Training ◽  
Sodium Nitroprusside ◽  
Coronary Arteries ◽  
Coronary Occlusion ◽  
Circumflex Coronary Artery ◽  
Miniature Swine ◽  
Chronic Occlusion ◽  
Chronic Coronary Occlusion ◽  
Camp And Cgmp

We previously reported that canine collateral-dependent coronary arteries exhibit impaired relaxation to adenosine but not sodium nitroprusside. In contrast, exercise training enhances adenosine sensitivity of normal porcine coronary arteries. These results stimulated the hypothesis that chronic coronary occlusion and exercise training produce differential effects on cAMP- versus cGMP-mediated relaxation. To test this hypothesis, Ameroid occluders were surgically placed around the proximal left circumflex coronary artery (LCx) of female Yucatan miniature swine 8 wk before initiating sedentary or exercise training (treadmill run, 16 wk) protocols. Relaxation to the cAMP-dependent vasodilators adenosine (10− 7 to 10− 3 M) and isoproterenol (3 × 10− 8 to 3 × 10− 5 M) were impaired in collateral-dependent LCx versus nonoccluded left anterior descending (LAD) arterial rings isolated from sedentary but not exercise-trained pigs. Furthermore, adenosine-mediated reductions in simultaneous tension and myoplasmic free Ca2+ were impaired in LCx versus LAD arteries isolated from sedentary but not exercise-trained pigs. In contrast, relaxation in response to the cAMP-dependent vasodilator forskolin (10− 9 to 10− 5 M) and the cGMP-dependent vasodilator sodium nitroprusside (10− 9 to 10− 4 M) was not different in LCx versus LAD arteries of sedentary or exercise-trained animals. These data suggest that chronic occlusion impairs receptor-dependent, cAMP-mediated relaxation; receptor-independent cAMP- and cGMP-mediated relaxation were unimpaired. Importantly, exercise training restores cAMP-mediated relaxation of collateral-dependent coronary arteries.

scholarly journals Contractile responsiveness of coronary arteries from exercise-trained rats

1997 ◽  
Vol 83 (2) ◽  
pp. 434-443 ◽  
Author(s):  
Janet L. Parker ◽  
Mildred L. Mattox ◽  
M. Harold Laughlin
Keyword(s):  
Nitric Oxide ◽  
Coronary Artery ◽  
Nitric Oxide Synthase ◽  
Exercise Training ◽  
Sodium Nitroprusside ◽  
Coronary Arteries ◽  
Internal Diameter ◽  
Relaxation Responses ◽  
Proximal Coronary Artery ◽  
Oxide Synthase

Parker, Janet L., Mildred L. Mattox, and M. Harold Laughlin.Contractile responsiveness of coronary arteries from exercise trained rats. J. Appl. Physiol. 83(2): 434–443, 1997.—The purpose of this study was to determine whether exercise training alters vasomotor reactivity of rat coronary arteries. In vitro isometric microvessel techniques were used to evaluate vasomotor properties of proximal left anterior artery rings (1 ring per animal) from exercise-trained rats (ET; n = 10) subjected to a 12-wk treadmill training protocol (32 m/min, 15% incline, 1 h/day, 5 days/wk) and control rats (C; n = 6) restricted to cage activity. No differences in passive length-tension characteristics or internal diameter (158 ± 9 and 166 ± 9 μm) were observed between vessesls of C and ET rats. Concentration-response curves to K+ (5–100 mM), prostaglandin F2α(10−8–10−4M), and norepinephrine (10−8–10−4) were unaltered ( P > 0.05) in coronary rings from ET rats compared with C rats; however, lower values of the concentration producing 50% of the maximal contractile response in rings from ET rats ( P = 0.05) suggest that contractile sensitivity to norepinephrine was enhanced. Vasorelaxation responses to sodium nitroprusside (10−9-10−4M) and adenosine (10−9-10−4M) were not different ( P > 0.05) between vessels of C and ET rats. However, relaxation responses to the endothelium-dependent vasodilator acetylcholine (ACh; 10−10-10−4M) were significantly blunted ( P < 0.001) in coronary rings from ET animals; maximal ACh relaxation averaged 90 ± 5 and 46 ± 12%, respectively, in vessels of C and ET groups. In additional experiments, two coronary rings (proximal and distal) were isolated from each C ( n = 7) and ET ( n = 7) animal. Proximal coronary artery rings from ET animals demonstrated decreased relaxation responses to ACh; however, ACh-mediated relaxation of distal coronary rings was not different between C and ET groups. N G-monomethyl-l-arginine (inhibitor of nitric oxide synthase) blocked ACh relaxation of all rings. l-Arginine (substrate for nitric oxide synthase) did not improve the blunted ACh relaxation in proximal coronary artery rings from ET rats. These studies suggest that exercise-training selectively decreases endothelium-dependent (ACh) but not endothelium-independent (sodium nitroprusside) relaxation responses of rat proximal coronary arteries; endothelium-dependent relaxation of distal coronary arteries is unaltered by training.

CHRONIC CORONARY OCCLUSION, EXERCISE TRAINING, AND PLASMA LIPIDS IN MINIATURE SWINE

2001 ◽  
Vol 33 (5) ◽  
pp. S214
Author(s):  
K Wooten ◽  
S E. Martin ◽  
J L. Parker ◽  
M Mattox ◽  
J Fogarty ◽  
...  
Keyword(s):  
Exercise Training ◽  
Coronary Occlusion ◽  
Plasma Lipids ◽  
Miniature Swine ◽  
Chronic Coronary Occlusion

scholarly journals Exercise training increases basal tone in arterioles distal to chronic coronary occlusion

2006 ◽  
Vol 290 (3) ◽  
pp. H1128-H1135 ◽  
Author(s):  
Cristine L. Heaps ◽  
Mildred L. Mattox ◽  
Katherine A. Kelly ◽  
Cynthia J. Meininger ◽  
Janet L. Parker
Keyword(s):  
Nitric Oxide ◽  
Exercise Training ◽  
Coronary Occlusion ◽  
External Solution ◽  
Nitric Oxide Production ◽  
Miniature Swine ◽  
Oxide Production ◽  
Chronic Coronary Occlusion ◽  
Basal Tone ◽  
Coronary Arterioles

Endurance exercise training increases basal active tone in coronary arteries and enhances myogenic tone in coronary arterioles of control animals. Paradoxically, exercise training has also been shown to augment nitric oxide production and nitric oxide-mediated relaxation in coronary arterioles. The purpose of the present study was to examine the effect of exercise training on basal active tone of arterioles (∼150 μm ID) isolated from the collateral-dependent region of hearts exposed to chronic coronary occlusion. Ameroid occluders were surgically placed around the proximal left circumflex coronary artery of miniature swine. Arterioles were isolated from both the collateral-dependent and nonoccluded myocardial regions of sedentary (pen confined) and exercise-trained (treadmill run; 14 wk) pigs. Coronary tone was studied in isolated arterioles using microvessel myographs and standard isometric techniques. Exposure to nominally Ca2+-free external solution reduced resting tension in all arterioles; decreases were most profound ( P < 0.05) in arterioles from the collateral-dependent region of exercise-trained animals. Furthermore, nitric oxide synthase (NOS) inhibition ( Nω-nitro-l-arginine methyl ester; 100 μM) unmasked markedly increased nitric oxide-sensitive tone in arterioles from the collateral-dependent region of exercise-trained swine. Blockade of K+ channels revealed significantly enhanced K+ channel contribution to basal tone in collateral-dependent arterioles of exercise-trained pigs. Protein content of endothelial NOS (eNOS) and phosphorylated eNOS (pS1179), determined by immunoblot, was elevated in arterioles from exercise-trained animals with the greatest effect in collateral-dependent vasculature. Taken together, we demonstrate the interaction of opposing exercise training-enhanced arteriolar basal active tone, nitric oxide production, and K+ channel activity in chronic coronary occlusion, potentially enhancing the capacity to regulate blood flow to collateral-dependent myocardium.

Altered reactivity of coronary arteries located distal to a chronic coronary occlusion

1997 ◽  
Vol 273 (4) ◽  
pp. H1879-H1887 ◽  
Author(s):  
Julie A. Rapps ◽  
Michael Sturek ◽  
Allan W. Jones ◽  
Janet L. Parker
Keyword(s):  
Nitric Oxide ◽  
Coronary Artery ◽  
Coronary Arteries ◽  
Adrenergic Receptor ◽  
Coronary Artery Occlusion ◽  
Canine Model ◽  
Contractile Responses ◽  
Chronic Occlusion ◽  
Chronic Coronary Occlusion

The coronary vasculature located distal to a chronic occlusion (collateral-dependent) has been shown to exhibit altered reactivity to vasoactive agonists. Thus we evaluated effects of chronic coronary artery occlusion on vasomotor responsiveness of collateral-dependent arteries isolated from a canine model of Ameroid occlusion of the left circumflex (LCX) coronary artery. We compared in vitro responses of large (∼1.3- to 1.4-mm-ID) and small (∼0.6-mm-ID) LCX arteries located distal to an occlusion with responses of similar-sized segments of the unoccluded left anterior descending (LAD) coronary artery. α-Adrenergic receptor-mediated contractile responses to norepinephrine (10−9–10−4M) and phenylephrine (10−9–10−4M) in the presence of propranolol were markedly enhanced in large LCX arteries compared with LAD arteries ( P< 0.001). Prazosin (1 μM), an α1-adrenergic receptor antagonist, abolished contractile responses of LCX and LAD arteries to norepinephrine. Inhibition of nitric oxide synthesis with N ω-nitro-l-arginine methyl ester (100 μM) enhanced norepinephrine-induced contractions of LAD arteries to a greater extent than contractions of LCX arteries. We simultaneously measured myoplasmic free Ca2+ (fura 2 fluorescence ratio) and contractile responses in LCX and LAD arteries denuded of endothelium; norepinephrine-induced increases in myoplasmic free Ca2+ and contractile tension were significantly enhanced in LCX arteries compared with LAD arteries. In addition, large and small LCX arteries exhibited impaired relaxation in response to adenosine (10−8–10−3M) compared with LAD arteries ( P < 0.05). In contrast, relaxation in response to the β-adrenergic agonist isoproterenol (10−9–10−4M) and sodium nitroprusside (10−10–10−4M) was not significantly different in LCX and LAD arteries. Thus collateral-dependent coronary arteries exhibit enhanced α-adrenergic vasoconstriction and impaired vasorelaxation in response to adenosine. The enhanced α-adrenergic contractile responsiveness involves at least two mechanisms: 1) enhanced α1-adrenergic reactivity of smooth muscle and 2) decreased α-adrenergic-induced synthesis of nitric oxide by the endothelium.

Exercise training improves endothelium-mediated vasorelaxation after chronic coronary occlusion

1999 ◽  
Vol 87 (5) ◽  
pp. 1948-1956 ◽  
Author(s):  
Kawanza L. Griffin ◽  
M. Harold Laughlin ◽  
Janet L. Parker
Keyword(s):  
Nitric Oxide ◽  
Coronary Artery ◽  
Nitric Oxide Synthase ◽  
Exercise Training ◽  
Coronary Occlusion ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Chronic Coronary Occlusion ◽  
Enhanced Production ◽  
Oxide Synthase

The present study evaluated combined effects of chronic coronary occlusion and exercise training on endothelial function. Gradual occlusion was produced by placement of an ameroid constrictor around the proximal left circumflex (LCX) coronary artery of female swine. Two months after placement of the ameroid, animals were restricted to their pens or exercise trained for 16 wk. Epicardial arteries (>500 μm ID) were isolated from the collateral-dependent LCX coronary artery distal to the occlusion and the nonoccluded left anterior descending (LAD) coronary artery. Bradykinin- and ADP-mediated relaxation of LCX and LAD coronary arteries was enhanced after exercise training. Inhibition of nitric oxide synthase with N G-nitro-l-arginine methyl ester decreased bradykinin- and ADP-mediated relaxation in LCX and LAD myocardial regions. Importantly, combined inhibition of effects of endothelium-derived hyperpolarizing factor with increased extracellular K+ (20–30 mM) and nitric oxide synthase completely abolished coronary LAD and LCX relaxation to bradykinin. Our data indicate that exercise training improves endothelium-mediated relaxation of arteries isolated after chronic coronary artery occlusion, likely as a result of enhanced production of nitric oxide and endothelium-derived hyperpolarizing factor.

Effects of exercise on collateral development in myocardial ischemia in pigs

1984 ◽  
Vol 56 (3) ◽  
pp. 656-665 ◽  
Author(s):  
C. M. Bloor ◽  
F. C. White ◽  
T. M. Sanders
Keyword(s):  
Coronary Artery ◽  
Myocardial Ischemia ◽  
Exercise Training ◽  
Collateral Circulation ◽  
Coronary Artery Stenosis ◽  
Arterial Stenosis ◽  
Collateral Flow ◽  
Circumflex Coronary Artery ◽  
Complete Occlusion ◽  
Collateral Development

To study the effects of exercise on collateral development in myocardial ischemia, we induced coronary arterial stenosis of the left circumflex coronary artery (LCCA) in 18 of 30 pigs. During that surgery, we identified the coronary bed at risk. Nine of these pigs were then subjected to 5 mo of exercise training on a treadmill. After exercise training, we determined regional collateral and myocardial blood flow using radiolabeled microspheres. At autopsy, all animals had complete occlusion of the LCCA. Infarct size in the exercise-trained pigs was significantly less than in the sedentary pigs (5.9 +/- 1.0 vs. 11.7 +/- 1.0% of the left ventricle). The exercise-trained animals had a greater increase in collateral flow, 35.1 +/- 3.0 vs. 28.7 +/- 4.1 ml X min-1 X 100 g-1, in the noninfarcted jeopardized zone of the LCCA bed. The major findings of the study were the following: 1) chronic coronary artery stenosis progressing to occlusion stimulated development of the collateral circulation and salvaged tissue in the jeopardized myocardium of an animal model with sparse collaterals; 2) development of the collateral circulation and tissue salvage is increased by exercise training; 3) collaterals develop primarily in or near the ischemic zone; and 4) all collateral beds develop a circumferential flow gradient following occlusion.

Gender influences coronary L-type Ca2+current and adaptation to exercise training in miniature swine

2001 ◽  
Vol 91 (6) ◽  
pp. 2503-2510 ◽  
Author(s):  
D. K. Bowles
Keyword(s):  
Smooth Muscle ◽  
Exercise Training ◽  
Endurance Training ◽  
Coronary Arteries ◽  
Current Density ◽  
Adaptive Response ◽  
Heart Weight ◽  
Internal Diameter ◽  
Resistance Arteries ◽  
Miniature Swine

Endurance exercise training increases smooth muscle L-type Ca2+current density in both resistance and proximal coronary arteries of female miniature swine. The purpose of the present study was to determine 1) whether gender differences exist in coronary smooth muscle (CSM) L-type Ca2+ current density and 2) whether endurance training in males would demonstrate a similar adaptive response as females. Proximal, conduit (∼1.0 mm), and resistance [∼200 μm (internal diameter)] coronary arteries were obtained from sedentary and treadmill-trained swine of both sexes. CSM were isolated by enzymatic digestion (collagenase plus elastase), and voltage-gated Ca2+-channel current ( I Ca) was determined by using whole cell voltage clamp during superfusion with 75 mM tetraethylammonium chloride and 10 mM BaCl2. Current-voltage relationships were obtained at test potentials from −60 to 70 mV from a holding potential of −80 mV, and I Ca was normalized to cell capacitance (pA/pF). Endurance treadmill training resulted in similar increases in heart weight-to-body weight ratio, endurance time, and skeletal muscle citrate synthase activity in male and female swine. I Ca density was significantly greater in males compared with females in both conduit (−7.57 ± 0.58 vs. −4.14 ± 0.47 pA/pF) and resistance arteries (−11.25 ± 0.74 vs. −6.49 ± 0.87 pA/pF, respectively). In addition, voltage-dependent activation of I Ca in resistance arteries was shifted to more negative membrane potentials in males. Exercise training significantly increased I Ca density in both conduit and resistance arteries in females (−7.01 ± 0.47 and −9.73 ± 1.13 pA/pF, respectively) but had no effect in males (−8.61 ± 0.50 and −12.04 ± 1.07 pA/pF, respectively). Thus gender plays a significant role in determining both the magnitude and voltage dependence of I Ca in CSM and the adaptive response of I Ca to endurance training.

Contrasting ischemic contraction patterns by zone and layer in canine myocardium

1982 ◽  
Vol 243 (6) ◽  
pp. H852-H855 ◽  
Author(s):  
S. Hattori ◽  
W. S. Weintraub ◽  
J. B. Agarwal ◽  
M. M. Bodenheimer ◽  
V. S. Banka ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Left Ventricle ◽  
Fiber Orientation ◽  
Coronary Occlusion ◽  
Short Axis ◽  
Circumflex Coronary Artery ◽  
Left Circumflex Coronary Artery ◽  
Close Relationship ◽  
Canine Myocardium

The effect of graded coronary occlusion on myocardial shortening in different zones of the left ventricle is not clear. Therefore, in 15 dogs ultrasonic crystals were used to evaluate the effect of graded coronary occlusion on subendocardial and subepicardial contraction in both the left anterior descending coronary artery (LAD) and left circumflex coronary artery (Circ) distributions. Subepicardial shortening was evaluated along both the long and short axes. In the LAD zones, segment shortening decreased in parallel in the subendocardium and subepicardium. In the circumflex zone subendocardial and subepicardial long axis shortening fell off in parallel, while subepicardial short axis shortening fell off more rapidly. Thus there is a close relationship between endocardial and epicardial segment shortening following graded coronary occlusion. In the circumflex zone, however, fiber orientation may affect the measurement of segment motion.

Effect of arteriolar dilation on coronary artery diameter distal to coronary stenoses

1985 ◽  
Vol 249 (5) ◽  
pp. H981-H988 ◽  
Author(s):  
J. S. Schwartz ◽  
R. J. Bache
Keyword(s):  
Regression Analysis ◽  
Coronary Artery ◽  
Coronary Occlusion ◽  
Circumflex Coronary Artery ◽  
Intracoronary Injection ◽  
Open Chest ◽  
Close Relationship ◽  
Coronary Artery Diameter ◽  
Coronary Stenoses ◽  
Chronically Instrumented Dogs

Previous studies have suggested that worsening hemodynamic severity of coronary stenoses in response to distal arteriolar dilation may be related to dilation of the normal epicardial artery adjacent to the stenosis resulting in increasing percent stenosis. To test this hypothesis we used sonomicrometry to continuously measure external circumflex coronary artery diameter distal to snare stenoses of varying severity in 19 open-chest dogs and 5 awake, chronically instrumented dogs. Arteriolar dilation produced by release of a transient coronary occlusion or by intracoronary injection of adenosine caused a decrease in circumflex coronary diameter distal to the stenosis. Regression analysis showed that circumflex diameter and pressure distal to the stenosis were directly related (mean r: transient occlusion, 0.86 +/- 0.04; adenosine, 0.97 +/- 0.01). The close relationship between pressure and diameter suggests that the decrease in diameter in response to arteriolar dilation was a passive effect. Passive coronary narrowing distal to a stenosis suggests that a similar effect may occur within a compliant stenosis, thus partly explaining the increase in severity of compliant stenoses in response to arteriolar dilation.

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