Nitric Oxide–mediated Relaxation to Lactate of Coronary Circulation in the Isolated Perfused Rat Heart

Montoya, Juan José; Fernández, Núria; Monge, Luis; Diéguez, Godofredo; Villalón, A. L. García

doi:10.1097/fjc.0b013e318226bcf7

Cited by 20 publications

(12 citation statements)

References 35 publications

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“…Endothelium-derived NO has been shown to play an important contributory role in the coronary vasodilatory response to a variety of physiological stimuli, including hypoxia, hypercapnia, and reactive hyperemia subsequent to transient occlusion 7. However, the effect of acid-base homeostasis and NO on vascular reactivity has been mainly studied in animal models 8…”

Section: Introductionmentioning

confidence: 99%

Effects of hypercapnia on peripheral vascular reactivity in elderly patients with acute exacerbation of chronic obstructive pulmonary disease

Matthaeis¹,

Greco²,

Dagostino³

et al. 2014

CIA

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Blood acid-base imbalance has important effects on vascular reactivity, which can be related to nitric oxide (NO) concentration and increased during hypercapnia. Release of NO seems to be linked to H+ and CO2 concentration and to exacerbation of chronic obstructive pulmonary disease (COPD), a common medical condition in the elderly. Flow-mediated dilation (FMD), a valuable cardiovascular risk indicator, allows assessment of endothelial-dependent vasodilation, which is to a certain extent mediated by NO. We investigated the effects of hypercapnia and acid-base imbalance on endothelial-dependent vasodilation by measurement of FMD in 96 elderly patients with acute exacerbation of COPD. Patients underwent complete arterial blood gas analysis and FMD measurement before (phase 1) and after (phase 2) standard therapy for acute exacerbation of COPD and recovery. Significant differences between phase 1 and phase 2 were observed in the mean values of pH (7.38±0.03 versus 7.40±0.02, P<0.001), pO2 (59.6±4.9 mmHg versus 59.7±3.6 mmHg, P<0.001), pCO2 (59.3±8.63 mmHg versus 46.7±5.82 mmHg, P<0.001), FMD (10.0%±2.8% versus 8.28%±2.01%, P<0.001) and blood flow rate (1.5±0.3 m/s versus 1.5±0.3 m/s, P=0.001). FMD values were positively correlated with pCO2 values (r=0.294, P=0.004) at baseline. A significant correlation was also found between relative changes in FMD and pCO2 levels, passing from phase 1 to phase 2 (r=0.23, P=0.023). Patients with higher baseline endothelium-dependent vasodilation as evaluated by FMD showed greater modification with regard to pCO2 changes (2.6±1.39 versus 1.59±1.4, P=0.012). In conclusion, endothelium-dependent vasodilation as evaluated by FMD was elevated during hypercapnia, and varied significantly according to pCO2 changes in patients with higher baseline levels, suggesting that vascular reactivity in acute COPD exacerbations in the elderly depends on integrity of the vascular endothelium.

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Section: Introductionmentioning

confidence: 99%

Effects of hypercapnia on peripheral vascular reactivity in elderly patients with acute exacerbation of chronic obstructive pulmonary disease

Matthaeis¹,

Greco²,

Dagostino³

et al. 2014

CIA

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“…Interestingly, lactate perfusion in MI hearts did not reduce cardiac perfusion pressure as we previously observed in isolated healthy hearts (5). We believe that it was in consequence of the MI-induced endothelium dysfunction, since Montoya et al (7) have previously demonstrated that lactate-induced vasodilation was endothelium-NO-dependent. Data obtained from lactate and pH levels, both in perfusate and cardiac tissue, suggest that the hearts were well-oxygenated and relying on aerobic metabolism.…”

Section: Discussionmentioning

confidence: 86%

“…Lactate also has an essential role in cardiac blood perfusion since it induces coronary artery relaxation. Montoya et al (7) showed that it caused vasodilation in isolated aortic rings and coronary arteries in a nitric oxide (NO)-dependent manner. We have also observed that lactate perfusion reduces cardiac perfusion pressure in healthy isolated hearts (5).…”

Section: Introductionmentioning

confidence: 99%

Lactate-upregulation of lactate oxidation complex-related genes is blunted in left ventricle of myocardial infarcted rats

Gabriel-Costa

Cunha

Paixão

et al. 2018

Braz J Med Biol Res

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Lactate modulates the expression of lactate oxidation complex (LOC)-related genes and cardiac blood flow under physiological conditions, but its modulatory role remains to be elucidated regarding pathological cardiac stress. The present study evaluated the effect of lactate on LOC-related genes expression and hemodynamics of hearts submitted to myocardial infarction (MI). Four weeks after MI or sham operation, isolated hearts of male Wistar rats were perfused for 60 min with Na+-lactate (20 mM). As expected, MI reduced cardiac contractility and relaxation with no changes in perfusion. The impaired cardiac hemodynamics were associated with increased reactive oxygen species (ROS) levels (Sham: 19.3±0.5 vs MI: 23.8±0.3 µM), NADPH oxidase (NOX) activity (Sham: 42.2±1.3 vs MI: 60.5±1.5 nmol·h−1·mg−1) and monocarboxylate transporter 1 (mct1) mRNA levels (Sham: 1.0±0.06 vs MI: 1.7±0.2 a.u.), but no changes in superoxide dismutase (SOD), catalase, NADH oxidase (NADox), and xanthine oxidase activities. Lactate perfusion in MI hearts had no additional effect on ROS levels, NADox, and NOX activity, however, it partially reduced mct1 mRNA expression (MI-Lactate 1.3±0.08 a.u.). Interestingly, lactate significantly decreased SOD (MI-Lactate: 54.5±4.2 µmol·mg−1·min−1) and catalase (MI: 1.1±0.1 nmol·mg−1·min−1) activities in MI. Collectively, our data suggest that under pathological stress, lactate lacks its ability to modulate the expression of cardiac LOC-related genes and the perfused pressure in hearts submitted to chronic MI. Together, these data contribute to elucidate the mechanisms involved in the pathogenesis of heart failure induced by MI.

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“…When the coronary vessel was precontracted by U46619, three injections produced more significant coronary vasodilatation than at basal tone in different physiological concentrations (1/800, 1/400 and 1/200). This modified vascular relaxation in the perfused heart attributes to the changes of artery tone [27]. However compared with SF injection and RG injection, RA injection did not demonstrate as strong as vasodilator effect unless hearts were pretreated by U46619.…”

Section: Discussionmentioning

confidence: 89%

The Coronary Dilation Effect of Shen Fu Injection Was Mediated through NO

Duan

et al. 2014

PLoS ONE

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ObjectivesShen Fu Injection (SF), which consisted of Red ginseng extraction injection (RG) and prepared aconite extraction injection (RA), is a traditional Chinese medicine mainly used for various cardiac diseases. This study is to analyse SF's effects on cardiac performance and coronary circulation. And the coronary dilating effect and mechanism of the above three injections were also explored.MethodsMature male guinea pigs were used as our animal model. We employed two types of perfusion methods (constant pressure and constant flow) in vitro, using Langendorff heart preparations to observe the cardiac function and coronary response to SF (1/200). The coronary dilation effects of the above three injections (1/800, 1/400 and 1/200) were recorded at basal coronary resting tone and when coronary vessels were pre-contracted with a thromboxane A2 analogue (U46619), in the presence or the absence of the inhibitor of nitric oxide synthesis (L-NAME, 10−4 M), the blocker of Ca2+-activated potassium channel(TEA, 10−3 M), or the blocker of adenosine triphosphate (ATP)-sensitive potassium channel (glybenclamide) (10−5 M).ResultsWhen perfused with constant pressure, SF significantly increased coronary flow, left ventricular developed pressure (LVDP) and the rate-pressure product (RPP). When perfused with constant flow, SF produced a significant reduction in the coronary perfusion pressure (CPP), LVDP and RPP. The coronary vasodilatation response of the above three injections can be reduced by L-NAME but was unaffected by TEA or glybenclamide when coronary vessels were pre-contracted with U46619 but not at resting tone. SF, RG and RA can all up-regulate eNOS expression in the human umbilical vein cells (EA.hy926).ConclusionWe demonstrated that SF does not contribute to the inotropic change of myocardium whose improvement is due to alternation of coronary flow. The coronary dilation effect of SF was mediated through RG and RA, via promoting NO release.

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Nitric Oxide–mediated Relaxation to Lactate of Coronary Circulation in the Isolated Perfused Rat Heart

Cited by 20 publications

References 35 publications

Effects of hypercapnia on peripheral vascular reactivity in elderly patients with acute exacerbation of chronic obstructive pulmonary disease

Effects of hypercapnia on peripheral vascular reactivity in elderly patients with acute exacerbation of chronic obstructive pulmonary disease

Lactate-upregulation of lactate oxidation complex-related genes is blunted in left ventricle of myocardial infarcted rats

The Coronary Dilation Effect of Shen Fu Injection Was Mediated through NO

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