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.

Chronic exercise training improves ACh-induced vasorelaxation in pulmonary arteries of pigs

2000 ◽  
Vol 88 (2) ◽  
pp. 443-451 ◽  
Author(s):  
Lynelle R. Johnson ◽  
Janet L. Parker ◽  
M. Harold Laughlin
Keyword(s):  
Nitric Oxide ◽  
Coronary Artery ◽  
Exercise Training ◽  
Pulmonary Arteries ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Chronic Exercise ◽  
Miniature Swine ◽  
Oxide Synthase ◽  
Surgically Induced

We hypothesized that exercise training would lead to enhanced endothelium-dependent vasodilation in porcine pulmonary arteries. Pulmonary artery rings (2- to 3-mm OD) were obtained from female Yucatan miniature swine with surgically induced coronary artery occlusion (ameroid occluder). Exercise training was performed for 16 wk, and vasomotor responses were studied by using standard isometric techniques. Contractile responses to 80 mM KCl, isosmotic KCl (10–100 mM), and norepinephrine (10−8 to 10−4 M) did not differ between sedentary (Sed) and exercise-trained (Ex) pigs. Relaxation was assessed to endothelium-dependent and endothelium-independent vasodilators after norepinephrine contraction. Pulmonary arteries of Ex pigs exhibited greater maximal relaxation to ACh (61.9 ± 3.5%) than did those of Sed pigs (52.3 ± 3.9%; P < 0.05). Endothelium-independent relaxation to sodium nitroprusside did not differ. Inhibition of nitric oxide synthase significantly decreased acetylcholine-induced relaxation, with greater inhibition in arteries from Ex pigs (P< 0.05). Inhibition of cyclooxygenase enhanced relaxation to acetylcholine in arteries from Sed pigs. We conclude that exercise training enhances endothelium-dependent (ACh-mediated) vasorelaxation in pulmonary arteries by mechanisms of increased reliance on nitric oxide and reduced production of a prostanoid constrictor.

scholarly journals Inducible nitric oxide synthase inhibits oxygen consumption in collateral-dependent myocardium

2014 ◽  
Vol 306 (3) ◽  
pp. H356-H362 ◽  
Author(s):  
Yingjie Chen ◽  
Ping Zhang ◽  
Jingxin Li ◽  
Xin Xu ◽  
Robert J. Bache
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Vascular Endothelial Cells ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Coordinated Expression ◽  
Collateral Vessels ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Following coronary artery occlusion growth of collateral vessels can provide an effective blood supply to the dependent myocardium. The ischemia, which results in growth of collateral vessels, recruits an inflammatory response with expression of cytokines and growth factors, upregulation of endothelial nitric oxide (NO) synthase (eNOS) in vascular endothelial cells, and expression of inducible nitric oxide synthase (iNOS) in both vessels and cardiac myocytes. Because NO is a potent collateral vessel dilator, this study examined whether NO derived from iNOS or constitutive NOS regulates myocardial blood flow (MBF) in the collateral region. Nonselective NOS inhibition with NG-nitro-l-arginine (LNA) caused vasoconstriction with a significant decrease in MBF to the collateral region during exercise. In contrast, the highly selective iNOS inhibitor 1400W caused a 21 ± 5% increase of MBF in the collateral region. This increase in MBF following selective iNOS blockade was proportionate to an increase in myocardial O2 consumption (MV̇o2). The results suggest that NO produced by iNOS inhibits MV̇o2 in the collateralized region, so that the increase in MBF following iNOS blockade was the result of metabolic vasodilation secondary to an increase in MV̇o2. Thus the coordinated expression of iNOS to restrain MV̇o2 and eNOS to maintain collateral vasodilation act to optimize the O2 supply-demand relationship and protect the collateralized myocardium from ischemia.

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.

scholarly journals Exercise training enhances multiple mechanisms of relaxation in coronary arteries from ischemic hearts

2013 ◽  
Vol 305 (9) ◽  
pp. H1321-H1331 ◽  
Author(s):  
Rachel R. Deer ◽  
Cristine L. Heaps
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Coronary Artery ◽  
Nitric Oxide Synthase ◽  
Exercise Training ◽  
Coronary Arteries ◽  
Vascular Function ◽  
Channel Inhibition ◽  
Oxide Synthase ◽  
Endothelium Dependent Relaxation

Exercise training of coronary artery disease patients is of considerable interest, since it has been shown to improve vascular function and, thereby, enhance blood flow into compromised myocardial regions. However, the mechanisms underlying exercise-induced improvements in vascular function have not been fully elucidated. We tested the hypothesis that exercise training increases the contribution of multiple mediators to endothelium-dependent relaxation of coronary arteries in the underlying setting of chronic coronary artery occlusion. To induce gradual occlusion, an ameroid constrictor was placed around the proximal left circumflex coronary artery in Yucatan miniature swine. At 8 wk postoperatively, pigs were randomly assigned to sedentary or exercise (treadmill, 5 days/wk) regimens for 14 wk. Exercise training significantly enhanced the contribution of nitric oxide, prostanoids, and large-conductance Ca2+-dependent K+ (BKCa) channels to endothelium-dependent, bradykinin-mediated relaxation in nonoccluded and collateral-dependent arteries. Combined nitric oxide synthase, prostanoid, and BKCa channel inhibition ablated the enhanced relaxation associated with exercise training. Exercise training significantly increased nitric oxide levels in response to bradykinin in endothelial cells isolated from nonoccluded and collateral-dependent arteries. Bradykinin treatment significantly increased PGI2 levels in all artery treatment groups and tended to be further enhanced after nitric oxide synthase inhibition in exercise-trained pigs. No differences were found in whole cell BKCa channel currents, BKCa channel protein levels, or arterial cyclic nucleotide levels. Although redundant, upregulation of parallel vasodilator pathways appears to contribute to enhanced endothelium-dependent relaxation, potentially providing a more refined control of blood flow after exercise training.

scholarly journals Effect of exercise training on nitric oxide and superoxide/H2O2 signaling pathways in collateral-dependent porcine coronary arterioles

2012 ◽  
Vol 112 (9) ◽  
pp. 1546-1555 ◽  
Author(s):  
Wei Xie ◽  
Janet L. Parker ◽  
Cristine L. Heaps
Keyword(s):  
Nitric Oxide ◽  
Coronary Artery ◽  
Exercise Training ◽  
Vascular Function ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Miniature Swine ◽  
Protein Levels ◽  
Endothelial Nitric Oxide ◽  
Coronary Arterioles

Endothelial nitric oxide (NO) synthase (NOS) has been shown to contribute to enhanced vascular function after exercise training. Recent studies have revealed that relatively low concentrations of reactive oxygen species can contribute to endothelium-dependent vasodilation under physiological conditions. We tested the hypothesis that exercise training enhances endothelial function via endothelium-derived vasodilators, NO and superoxide/H2O2, in the underlying setting of chronic coronary artery occlusion. An ameroid constrictor was placed around the proximal left circumflex coronary artery to induce gradual occlusion in Yucatan miniature swine. At 8 wk postoperatively, pigs were randomly assigned to sedentary (pen-confined) or exercise-training (treadmill-run: 5 days/wk for 14 wk) regimens. Exercise training significantly enhanced concentration-dependent, bradykinin-mediated dilation in cannulated collateral-dependent arterioles (∼130 μm diameter) compared with sedentary pigs. NOS inhibition reversed training-enhanced dilation at low bradykinin concentrations in collateral-dependent arterioles, although increased dilation persisted at higher bradykinin concentrations. Total and phosphorylated (Ser1179) endothelial NOS protein levels were significantly increased in arterioles from collateral-dependent compared with the nonoccluded region, independent of exercise. The H2O2 scavenger polyethylene glycol-catalase abolished the training-enhanced bradykinin-mediated dilation in collateral-dependent arterioles; similar results were observed with the SOD inhibitor diethyldithiocarbamate. Fluorescence measures of bradykinin-stimulated H2O2 levels were significantly increased by exercise training, independent of occlusion. The NADPH inhibitor apocynin significantly attenuated bradykinin-mediated dilation in arterioles of exercise-trained, but not sedentary, pigs and was associated with significantly increased protein levels of the NADPH subunit p67phox. These data provide evidence that, in addition to NO, the superoxide/H2O2 signaling pathway significantly contributes to exercise training-enhanced endothelium-mediated dilation in collateral-dependent coronary arterioles.

scholarly journals Chronic coronary artery occlusion: when does the benefit outweigh the risk?

2019 ◽  
pp. 116-123
Author(s):  
A. G. Badoyan ◽  
D. A. Khelimsky ◽  
A. A. Shermuk ◽  
O. V. Krestyaninov ◽  
A. S. Bobrova ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Coronary Artery ◽  
Coronary Occlusion ◽  
Interventional Cardiology ◽  
Coronary Artery Occlusion ◽  
Evidence Base ◽  
Artery Occlusion ◽  
Endovascular Recanalization ◽  
Chronic Coronary Occlusion

Today, the treatment of patients with chronic coronary occlusion is one of the most difficult problems in interventional cardiology. This is due not only to the technical difficulties of endovascular recanalization, but also to the difficulty in selecting patients for whom revascularization will be beneficial. Due to the low evidence base and the conflicting results of large clinical trials, these patients are rarely referred for endovascular recanalization. The purpose of this article is to review the literature and systematize relevant knowledge on the management of patients with chronic coronary occlusion.

Changes in Arginase-Nitric Oxide Synthase System at Adaptation to Prolonged Exercise Training by Swimming in Adult and Aged Rat Hearts

2012 ◽  
Vol 3 (4) ◽  
pp. 299-308 ◽  
Author(s):  
Anatolii V. Kotsuruba ◽  
Yulia P. Korkach ◽  
Sergey O. Talanov ◽  
Olga V. Bazilyuk ◽  
Lyubov G. Stepanenko ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Exercise Training ◽  
Prolonged Exercise ◽  
Aged Rat ◽  
Rat Hearts ◽  
Oxide Synthase
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