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 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.

Endothelium-dependent relaxations in canine coronary arteries are enhanced in early heart failure and persist in recovery

1994 ◽  
Vol 72 (10) ◽  
pp. 1148-1154 ◽  
Author(s):  
Giulia Larosa ◽  
Paul W. Armstrong ◽  
Christine Forster
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Coronary Artery ◽  
Coronary Arteries ◽  
Early Onset ◽  
Contractile Responses ◽  
Acetylcholine Sensitivity ◽  
Coronary Endothelium ◽  
Functional Relaxation

In vitro coronary artery responsiveness to noradrenaline, phenylephrine, and BHT-920 together with functional relaxation to acetylcholine was assessed in dogs at the early onset of pacing-induced heart failure (1 week) and in dogs recovered from heart failure (3 weeks paced, followed by 4 weeks discontinued pacing). α-Adrenoceptor stimulation produced contractile responses that were unaltered in early congestive heart failure and recovery. Contractions to noradrenaline and BHT-920 were always less than those produced by phenylephrine. Endothelium-intact arteries demonstrated relaxations in response to noradrenaline and BHT-920, but not phenylephrine. Relaxations to noradrenaline were enhanced 24% in early heart failure and 47% following recovery from heart failure, compared with control. BHT-920 produced relaxations that were augmented 21 and 76% in early heart failure and recovery, respectively. Contractile sensitivity to noradrenaline increased 5-fold in early heart failure and was not different in recovery, compared with control. Contractile sensitivity to BHT-920 and phenylephrine was unaltered throughout. Acetylcholine produced relaxations that were increased 21% in early heart failure and 13% after recovery from congestive heart failure. Furthermore, acetylcholine sensitivity was significantly enhanced in early heart failure and recovery. The current study reveals a progressive adaptation of the coronary endothelium in congestive heart failure, possibly directed towards protection against excessive vasoconstriction due to circulating catecholamines.Key words: endothelium, congestive heart failure, coronary arteries, α-adrenoceptors, noradrenaline, acetylcholine.

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.

Recombinant Gene Transfer of Endothelial Nitric Oxide Synthase Augments Coronary Artery Relaxations During Hypoxia

Circulation ◽  
1999 ◽  
Vol 100 (suppl_2) ◽  
Author(s):  
David G. Cable ◽  
Vincent J. Pompili ◽  
Timothy O’Brien ◽  
Hartzell V. Schaff
Keyword(s):  
Nitric Oxide ◽  
Coronary Artery ◽  
Nitric Oxide Synthase ◽  
Gene Transfer ◽  
Coronary Arteries ◽  
Endothelial Nitric Oxide Synthase ◽  
No Production ◽  
Viral Control ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Background —Coronary arteries respond to hypoxia with transient relaxations, which increases coronary blood flow, in part, by release of nitric oxide. We hypothesized that increased expression of nitric oxide synthase might further augment blood vessel relaxation during hypoxia. The present study examined the effect of adenovirus-mediated transfer of bovine endothelial nitric oxide synthase (eNOS) on hypoxia-induced transient relaxations in canine coronary arteries. Methods and Results —Paired segments of coronary arteries were exposed to vehicle (phosphate-buffered saline with albumin) or an adenovirus encoding either E coli β-galactosidase (Ad.CMVLacZ, viral control; 10 10 pfu/mL) or eNOS (Ad.CMVeNOS; 10 10 pfu/mL) for 2 hours at 37°C. Immunohistochemistry with a monoclonal antibody specific for eNOS documented both endothelial and adventitial expression in Ad.CMVeNOS arteries, whereas vehicle and viral controls demonstrated only constitutive expression. Levels of cGMP were increased 5-fold in Ad.CMVeNOS arteries compared with controls. In arteries exposed to Ad.CMVeNOS, maximum contraction to prostaglandin F 2α was reduced compared with viral controls, and this effect was eliminated by pretreatment with a competitive inhibitor of eNOS ( N G -monomethyl- l -arginine, 10 −3 mol/L). Hypoxia-induced transient relaxation (95% N 2 -5% CO 2 ) in Ad.CMVeNOS arteries (45.2±8.8%, n=6) was augmented compared with vehicle (26.3±6.0%) or viral (27.2±7.1%) controls. Conclusions —Adenovirus-mediated gene transfer of nitric oxide synthase reduces receptor-dependent contractions and augments hypoxia-induced relaxations in canine coronary arteries; this method of augmentation of NO production might be advantageous for reduction of coronary artery vasospasm.

Coexistence and outcome of coronary artery disease in Takotsubo syndrome

2020 ◽  
Vol 41 (34) ◽  
pp. 3255-3268 ◽  
Author(s):  
L Christian Napp ◽  
Victoria L Cammann ◽  
Milosz Jaguszewski ◽  
Konrad A Szawan ◽  
Manfred Wischnewsky ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Coronary Arteries ◽  
Coronary Artery Occlusion ◽  
Coronary Intervention ◽  
Artery Occlusion ◽  
Takotsubo Syndrome ◽  
Normal Coronary Arteries ◽  
Coronary Syndrome ◽  
Artery Disease

Abstract Aims Takotsubo syndrome (TTS) is an acute heart failure syndrome, which shares many features with acute coronary syndrome (ACS). Although TTS was initially described with angiographically normal coronary arteries, smaller studies recently indicated a potential coexistence of coronary artery disease (CAD) in TTS patients. This study aimed to determine the coexistence, features, and prognostic role of CAD in a large cohort of patients with TTS. Methods and results Coronary anatomy and CAD were studied in patients diagnosed with TTS. Inclusion criteria were compliance with the International Takotsubo Diagnostic Criteria for TTS, and availability of original coronary angiographies with ventriculography performed during the acute phase. Exclusion criteria were missing views, poor quality of angiography loops, and angiography without ventriculography. A total of 1016 TTS patients were studied. Of those, 23.0% had obstructive CAD, 41.2% had non-obstructive CAD, and 35.7% had angiographically normal coronary arteries. A total of 47 patients (4.6%) underwent percutaneous coronary intervention, and 3 patients had acute and 8 had chronic coronary artery occlusion concomitant with TTS, respectively. The presence of CAD was associated with increased incidence of shock, ventilation, and death from any cause. After adjusting for confounders, the presence of obstructive CAD was associated with mortality at 30 days. Takotsubo syndrome patients with obstructive CAD were at comparable risk for shock and death and nearly at twice the risk for ventilation compared to an age- and sex-matched ACS cohort. Conclusions Coronary artery disease frequently coexists in TTS patients, presents with the whole spectrum of coronary pathology including acute coronary occlusion, and is associated with adverse outcome. Trial registration ClinicalTrials.gov number: NCT01947621.

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 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 Enhanced KCl-mediated contractility and Ca2+ sensitization in porcine collateral-dependent coronary arteries persist after exercise training

2020 ◽  
Vol 319 (4) ◽  
pp. H915-H926
Author(s):  
Cristine L. Heaps ◽  
Jeff F. Bray ◽  
Janet L. Parker
Keyword(s):  
Exercise Training ◽  
Coronary Arteries ◽  
Rho Kinase ◽  
Metabolic Demand ◽  
Contractile Responses ◽  
Calcium Sensitization ◽  
Channel Current ◽  
Chronic Occlusion ◽  
Flow Reserve ◽  
Arterial Tone

Small coronary arteries distal to chronic occlusion displayed enhanced contractile responses, which were further augmented after exercise training and attributable to enhanced calcium sensitization without alterations in calcium channel current. The calcium sensitization mediators Rho-kinase and CaMKII significantly contributed to enhanced contraction in collateral-dependent arteries of exercise-trained, but not sedentary, pigs. Exercise-enhanced contractile responses may increase resting arterial tone, creating an enhanced coronary flow reserve that is accessible during periods of increased metabolic demand.

scholarly journals A1A-ADRENERGIC RECEPTOR OVEREXPRESSION PROTECTS AGAINST THE DEVELOPMENT OF ARRHYTHMIAS FOLLOWING CORONARY ARTERY OCCLUSION

2017 ◽  
Vol 69 (11) ◽  
pp. 465
Author(s):  
John Guers ◽  
Seonghun Yoon ◽  
Jie Zhang ◽  
Xin Zhao ◽  
Dorothy E. Vatner ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Adrenergic Receptor ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion
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