Protection Against Ischemic Injury by Nonvasoactive Concentrations of Nitric Oxide Synthase Inhibitors in the Perfused Rabbit Heart

Depré, Christophe; Vanoverschelde, Jean–Louis; Goudemant, Jean-François; Mottet, Isabelle; Hue, Louis

doi:10.1161/01.cir.92.7.1911

Cited by 125 publications

(59 citation statements)

References 40 publications

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“…[80][81][82] The decline of glucose uptake during prolonged severe ischemia may be attenuated by various interventions protecting the heart against ischemic injury, such as an increase of the extracellular glucose concentration or the addition of insulin. [82][83][84][85][86] The stimulation of glucose uptake by moderate ischemia is additive to that induced by insulin. 87 These interventions promote glucose uptake to meet the increased demand for glucose moieties as an energy source.…”

Section: Glucose Metabolism In the Ischemic And Reperfused Heartmentioning

confidence: 99%

“…101 Thus, cGMP probably downregulates glucose uptake during ischemia, as the addition of NO synthase inhibitors to ischemic heart stimulates glucose metabolism and improves the resistance against ischemia. 83 …”

Section: Glucose Uptakementioning

confidence: 99%

“…In isolated perfused hearts subjected to low-flow ischemia, glycogen breakdown provides, during the first 15 minutes, about 60 mol glucose equivalents per gram dry weight, whereas during the same period, glucose uptake offers about 35 mol glucose per gram. 83 In the same model, ischemic contracture begins when glycogen breakdown stops and, concomitantly, the rate of glucose uptake decreases. Enhanced utilization of extracellular glucose during ischemia does not increase the absolute rate of glycolytic flux but prevents the participation of glycogen stores to this flux, thereby limiting ischemic damage and contracture.…”

Section: Glycogen Metabolismmentioning

confidence: 99%

See 2 more Smart Citations

Glucose for the Heart

Depré¹,

Vanoverschelde²,

Taegtmeyer³

1999

Circulation

380

260

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Section: Glucose Metabolism In the Ischemic And Reperfused Heartmentioning

confidence: 99%

Section: Glucose Uptakementioning

confidence: 99%

Section: Glycogen Metabolismmentioning

confidence: 99%

See 1 more Smart Citation

Glucose for the Heart

Depré¹,

Vanoverschelde²,

Taegtmeyer³

1999

Circulation

380

260

View full text Add to dashboard Cite

“…One such mechanism may follow from the observation that NO regulates Ca2+ current in cardiomyocytes (33). NO may also reduce myocardial oxygen consumption (34) as a result of a direct negative inotropic effect, inhibition of norepinephrine release from sympathetic nerve terminals, and/or an increase in ATP generation by stimulation of glycolysis (35). In addition to the energy-sparing effects of NO on the myocardium, cGMP-mediated coronary vasodilation may help to reduce myocardial ischemia.…”

Section: Effects Of Ace Inhibitors On Myocardial Infarct Sizementioning

confidence: 99%

Cellular Mechanisms of Cardioprotection Afforded by Inhibitors of Angiotensin Converting Enzyme in Ischemic Hearts: Role of Bradykinin and Nitric Oxide.

et al. 2000

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Angiotensin converting enzyme (ACE) inhibitors inhibit the degradation of bradykinin and contribute to accumulation of bradykinin and NO, both of which may be beneficial for diseased hearts. To test this idea, we administered imidaprilat and cilazaprilat, respectively to the canine ischemic myocardium. In the open chest dogs with low constant coronary perfusion pressure (CPP, from 104 ± 3 to 42 ± 3 mmHg), coronary blood flow (CBF, 91 ± 1 to 32 ± 2 mI/100 g/min), fractional shortening (FS), and lactate extraction ratio (LER) decreased. Either imidaprilat or cilazaprilat increased CBF, FS, and LER with increases in cardiac bradykinin and NO levels. The beneficial effects of ACE inhibitors were blunted by either L-NAME (an inhibitor of NO synthase) and HOE140 (an inhibitor of bradykinin receptors), respectively. ACE inhibitors, on the other hand, are reported to attenuate the severity of myocardial stunning, which effect is partially attributable to bradykinin-and NO-dependent mechanisms.Further, ACE inhibitors limited infarct size following coronary occlusion and reperfusion. This infarct size-limitation was blunted by either L-NAME and IBTX (the antagonist of KCa channels). Bradykinin is also reported to close Kca channels. Thus, we concluded that ACE inhibitors attenuate both reversible and irreversible myocardial cellular injury via bradykinin/NOdependent mechanisms. In experimental and clinical settings, the cardioprotective effects of ACE inhibitors on the diseased heart may be attributable to these mechanisms. (Hypertens Res 2000; 23: 253-259)

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“…However, t-PA has been reported to activate inducible nitric oxide synthase (iNOS) [44], which acts to increase the levels of nitric oxide (NO). In turn, NO has been associated with a reduction in myocardial contractility by uncoupling of calcium metabolism [45,46], through effects on glucose metabolism [46], and through a reduction in -adrenergic responsiveness [47]. Furthermore, NO induce vasodilatation, thereby decreasing coronary perfusion pressure and systemic perfusion [3].…”

Section: Discussionmentioning

confidence: 99%