Preconditioning of the ischaemic myocardium; involvement of the <scp>l</scp>‐arginine nitric oxide pathway

Végh, Ágnes; Szekeres, L.; Parratt, J. R.

doi:10.1111/j.1476-5381.1992.tb14501.x

Cited by 238 publications

(166 citation statements)

References 19 publications

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“…Among these substances, NO has been recognised as having pronounced beneficial effects, owing to its powerful vasodilator action (Rubanyi et al, 1991;Vegh et al, 1992). The newly recognised property of RLX to stimulate NO production in perfused hearts suggests that this hormone may play an important role in the regulation of myocardial perfusion.…”

Section: Discussionmentioning

confidence: 99%

Relaxin‐induced increased coronary flow through stimulation of nitric oxide production

Bani-Sacchi

Bigazzi²,

Bani

et al. 1995

British J Pharmacology

152

125

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1 Relaxin (RLX) is a multifunctional hormone which, besides its role in pregnancy and parturition, has also been shown to influence the cardiovascular system. In this study, we investigated the effect of RLX on coronary flow of rat and guinea-pig hearts, isolated and perfused in a Langendorff apparatus. RLX was either added to the perfusion fluid at a concentration of 5 x 109 M for a 20-min perfusion, or given as a bolus into the aortic cannula at concentrations of 10-9 M, 5 x io-9 M and 10-8 M dissolved in 1 ml of perfusion fluid. 2 RLX, given either for a 20-min perfusion or as a bolus in the aortic cannula to guinea-pig and rat isolated hearts, increased the coronary flow and the amount of nitrite, a stable end-product of nitric oxide (NO) metabolism, that appeared in the perfusates in a concentration-dependent fashion. 3 The increase in coronary flow and in nitrite in the perfusates induced by RLX was significantly reduced by pretreatment with the nitric oxide synthase (NOS) 4 The effects of RLX on coronary flow and nitrite amounts in the perfusates were compared with those induced by the endothelium-dependent vasodilator agent, acetylcholine (ACh, I0--I0-M), and by the endothelium-independent vasodilator agent, sodium nitroprusside (SNP, I0--10-6 M). The results obtained show that RLX is more effective than ACh and SNP in increasing coronary flow. 5 The results of this study show that RLX increases coronary flow through stimulation of NO production; hence this hormone should be regarded as a novel agent capable of improving myocardial perfusion.

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Section: Discussionmentioning

confidence: 99%

Relaxin‐induced increased coronary flow through stimulation of nitric oxide production

Bani-Sacchi

Bigazzi²,

Bani

et al. 1995

British J Pharmacology

152

125

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“…Along this line, potential mediators include nitric oxide (NO) 2,4 and adenosine. 5 Vegh et al 6 reported that the protection conferred by preconditioning in dog heart in vivo disappeared after NO inhibition. Nevertheless, other authors 7 found that endogenous NO is not a mediator in the ischemic preconditioning in the isolated rat heart.…”

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confidence: 99%

Hepatic preconditioning in rats is defined by a balance of adenosine and xanthine

et al. 1998

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The present work investigates the relationship between adenosine, nitric oxide (NO), and free radicals during ischemic preconditioning in rat liver. For this purpose, we evaluated: 1) the efficacy of different periods of preconditioning; 2) the changes in the concentration of adenine nucleotides during preconditioning; 3) the importance of adenosine and xanthine concentrations in the induction of preconditioning; and 4) the possible effect of xanthine oxidase-derived superoxide anion on NO during preconditioning. Results show that just a 10-to 15-minute period of ischemia followed by 10-minute reperfusion prevents the ischemic damage that would be induced by a subsequent 90 minutes of ischemia followed by 90 minutes of reperfusion. Administration of xanthine or metabolization of endogenous adenosine abolishes the protective effect of preconditioning. When rats have been subjected to a period of preconditioning not within the effective time window (10-15 minutes), and thus offering no protection, the administration of a NO donor was found to restore the protection. The dose needed to restore protection appears to be proportional to the endogenous xanthine concentration. In addition, when xanthine oxidase was inhibited, preconditioning effectively offered protection in front of ischemia and reperfusion, independently of the xanthine concentration. Altogether, this indicates that the time window of ischemia capable to induce preconditioning in liver is defined by the relative tissue concentrations of adenosine and xanthine. The lower limit of this window (10 minutes) is defined by the amount of adenosine able to induce NO generation. Its upper limit (15 minutes) is defined by the concentration of xanthine able to remove the generated NO. (HEPATOLOGY 1998;28:768-773.)In 1986, Murry et al. discovered that short periods of ischemia and reperfusion render the myocardium resistant to a subsequent more-sustained ischemic insult. 1 This phenomenon, called ischemic preconditioning, has been commonly studied in the heart, but few studies have been performed on intestine 2 or liver. 3 The mechanism underlying preconditioning remains unknown and is currently under intense investigation. It has been suggested that protection depends on the release of substances by the organ helping to protect it against injury. Along this line, potential mediators include nitric oxide (NO) 2,4 and adenosine. 5 Vegh et al. 6 reported that the protection conferred by preconditioning in dog heart in vivo disappeared after NO inhibition. Nevertheless, other authors 7 found that endogenous NO is not a mediator in the ischemic preconditioning in the isolated rat heart. Recent work by our group, using a model of hepatic preconditioning in rat, demonstrated that inhibition of NO abolishes the effect of preconditioning. 8 In the same study, we suggested that NO production was stimulated by endogenous adenosine. It is known that pretreatment with adenosine or selective adenosine A 1 receptor agonists mimics the effect of preconditioning in heart. 10 Bot...

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“…Furthermore, since many of the beneficial effects of statins are thought to be mediated via the synthesis of nitric oxide (Laufs et al, 1997;Laufs and Liao, 1998), and since we have a number of previous evidence that NO plays an essential role in the protection against the ischaemia-induced early arrhythmias (e.g. Végh et al, 1992b;Kis et al, 1999), we have now also examined whether the effect of simvastatin on arrhythmias involves the activation of eNOS and the subsequent increase in NO formation.…”

Section: Discussionmentioning

confidence: 99%

“…We have substantial previous evidence that NO plays an essential role in both the early and delayed anti-arrhythmic effects of preconditioning, induced either by brief periods of coronary artery occlusion (Végh et al, 1992b), cardiac pacing (Kis et al, 1999) or heavy physical exercise (Babai et al, 2002). We hypothesized that these preconditioning stimuli, via the activation of eNOS, enhance NO production and modify myocardial function during ischaemia and reperfusion (Parratt and Végh, 1996).…”

Section: Introductionmentioning

confidence: 99%

The effect of acute simvastatin administration on the severity of arrhythmias resulting from ischaemia and reperfusion in the canine: Is there a role for nitric oxide?

Kisvári

Kovács

Gardi

et al. 2014

European Journal of Pharmacology

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a b s t r a c tThe present study has examined the effects and the possible mechanisms of a single dose of simvastatin on the severity of arrhythmias resulting from a 25 min occlusion and reperfusion of the left anterior descending coronary artery in anaesthetized (chloralose and urethane) dogs. The control animals (n ¼16) were given the solvent of simvastatin by slow (over 5 min) intracoronary (ic.) injection just prior to the occlusion. Twenty-six dogs were treated with simvastatin (0.1 mg/kg) by the same route, both in the absence (n ¼15) and in the presence (n ¼11) of L-NAME. This latter was administered (5 mg/kg, ic.) either alone (n ¼12) or 10 min before the simvastatin treatment. The severity of ischaemia (epicardial STsegment, inhomogeneity) and ventricular arrhythmias (ventricular premature beats [VPBs], ventricular tachycardia [VT] and fibrillation [VF]), plasma nitrite/nitrate levels, myocardial superoxide production and eNOS activity were assessed. Compared with controls simvastatin significantly reduced the number of VPBs (289 7 34 vs. 947 25) and the episodes of VT (5.67 1.3 vs. 0.3 70.2), the incidence of VT (88% vs. 20%) and VF (56% vs. 0%) during occlusion and increased survival (0% vs. 33%) on reperfusion. There were also less marked ischaemic changes in the simvastatin-treated dogs than in the controls. Simvastatin preserved eNOS activity and nitric oxide (NO) bioavailability during occlusion and attenuated superoxide production following reperfusion. All these effects of simvastatin (except for the protection against VF) were reversed by L-NAME. We conclude that simvastatin given just prior to ischaemia/reperfusion reduces the severity of arrhythmias. This effect involves both NO-dependent and NO-independent mechanisms.

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Preconditioning of the ischaemic myocardium; involvement of the l‐arginine nitric oxide pathway

Cited by 238 publications

References 19 publications

Relaxin‐induced increased coronary flow through stimulation of nitric oxide production

Relaxin‐induced increased coronary flow through stimulation of nitric oxide production

Hepatic preconditioning in rats is defined by a balance of adenosine and xanthine

The effect of acute simvastatin administration on the severity of arrhythmias resulting from ischaemia and reperfusion in the canine: Is there a role for nitric oxide?

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