Early preconditioning prevents the loss of endothelial nitric oxide synthase and enhances its activity in the ischemic/reperfused rat heart

Muscari, Claudio; Bonafè, Francesca; Gamberini, Chiara; Giordano, Emanuele; Tantini, Benedetta; Fattori, Monia; Guarnieri, Carlo; Caldarera, Claudio Marcello

doi:10.1016/j.lfs.2003.10.001

Cited by 25 publications

(18 citation statements)

References 37 publications

(40 reference statements)

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“…The abolition of preconditioning by L-NAME (but not selective nNOS nor iNOS inhibition) suggests that NO produced by eNOS is a key mediator of IPC in attenuating I/R-induced leukocyte -endothelium interactions. Our results are consistent with the findings of Laude et al 46 and Muscari et al 47 who both suggested that NO produced by eNOS may play an important role in early and/or delayed preconditioning. However, there is still a possibility that NO derived from any 1 of 3 isoforms of NOS is sufficient to mediate the protective effect of IPC and that all 3 isoforms of NOS must be simultaneously inhibited to abrogate the protective effect of IPC, which may be consistent with the finding of upregulation of all 3 NOS during I/R + IPC (Fig 3).…”

Section: Discussionsupporting

confidence: 94%

Ischemic Preconditioning Attenuates Postischemic Leukocyte - Endothelial Cell Interactions Role of Nitric Oxide and Protein Kinase C

Huang

Wei

Hung

2006

Circ J

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Section: Discussionsupporting

confidence: 94%

Ischemic Preconditioning Attenuates Postischemic Leukocyte - Endothelial Cell Interactions Role of Nitric Oxide and Protein Kinase C

Huang

Wei

Hung

2006

Circ J

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“…Changes in eNOS protein expression seem to be at least partly related to those of cNOS activities. Most recently, Muscari et al (2004) demonstrated that cardiac IP inhibits the loss of eNOS protein expression and enhances its activity in rat hearts exposed to I/R. We also observed that eNOS protein expression was increased in the postischemic rat kidney with IP treatment (Yamashita et al, 2003).…”

Section: Enos and Renal Ischemic Preconditioningmentioning

confidence: 51%

Endothelial Nitric Oxide Contributes to the Renal Protective Effects of Ischemic Preconditioning

Yamasowa¹,

Shimizu²,

Inoué³

et al. 2004

J Pharmacol Exp Ther

102

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We determined whether endothelial nitric oxide synthase (eNOS) plays an important role in the renal protective effect of ischemic preconditioning (IP) against the ischemia/reperfusioninduced acute renal failure (ARF) by using eNOS-deficient (eNOS Ϫ/Ϫ ) and wild-type (eNOS ϩ/ϩ ) mice. Ischemic ARF was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. IP, which consists of three cycles of 2-min ischemia followed by 5-min reperfusion, was performed prior to 45-min ischemia. In eNOS ϩ/ϩ mice, IP treatment markedly attenuated the ischemia/reperfusion-induced renal dysfunction and significantly improved histological renal damage such as tubular necrosis, proteinaceous casts in tubuli, and medullary congestion. Constitutive nitric oxide synthase activity in the kidney without IP was markedly decreased 6 h after reperfusion, but this decreased response was not observed in eNOS ϩ/ϩ mice with IP treatment. The improvement of renal dysfunction in eNOS ϩ/ϩ mice with IP treatment was abolished by pretreatment with N G -nitro-L-arginine, a nonselective NOS inhibitor, whereas aminoguanidine, an inducible NOS inhibitor, had no effect. Finally, no protective effects of IP on ischemia/reperfusion-induced renal dysfunction and histological damage were observed in eNOS Ϫ/Ϫ mice. These findings strongly support the view that eNOS-mediated NO production plays a pivotal role in the protective effect of IP on ischemia/reperfusion-induced ARF.

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“…Nevertheless, our results, obtained from the parallel measurement of NOS activation and products, which is an advantage of this study, clearly demonstrated that PC preserves the function of NOS and, as a result of it, increases NO bioavailability and decreases superoxide production during a subsequent prolonged period of occlusion. This finding confirms the previous observations in rat isolated hearts that PC prevents the loss of NOS enzymes and enhances NOS activity during ischaemia and reperfusion (Muscari et al, 2004).…”

Section: Study IIsupporting

confidence: 93%

Further evidence for the role of nitric oxide in the antiarrhythmic effect of ischaemic preconditioning: the effect of peroxynitrite and changes in NOS-dependent NO production

Juhász¹

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(Kiss et al., 2008). This study, however, did not examine whether PN, generated during the brief periods of preconditioning I/R insults, plays also a trigger role in the PC-induced antiarrhythmic protection. Therefore, in the first series of experiments (Study I) we examined this by the use of uric acid (UA; 0.2 mg/kg/min, over 30 min), a relatively selective scavenger of PN, and the effects obtained in PC dogs were compared to those dogs that had been received PN exogenously, 25 min before the occlusion of the left anterior descending coronary artery (LAD). In these experiments the severity of ischaemia and of ventricular arrhythmias, changes in plasma nitrate/nitrite (NOx) levels, as well as myocardial superoxide and nitrotyrosine (NT) production (a marker of PN generation) were assessed.We have found that both the PC procedure (2x5 min occlusion/reperfusion) and the administration of PN resulted in a significant increase in NT formation, which was abolished or markedly attenuated in the presence of UA. This attenuation of PN formation in PC dogs, however, did not influence the PC-induced protection; i.e. the number and the incidence of ventricular arrhythmias during the prolonged occlusion remained to be suppressed, whereas the increase in NO bioavailability and the decrease in superoxide production were as the same as in the PC animals. In contrast, UA completely abrogated the protection that resulted from the administration of PN. Interestingly, UA itself also reduced the arrhythmias; an effect which might be associated with the antioxidant property of the compound. Our conclusion was that PN administration results in a PC-like protection against arrhythmias, but PN, generated during the PC procedure, is not necessary for triggering the PC-induced antiarrhythmic protection.The second series of experiments (Study II) aimed to examine whether the increased NO bioavailability that occurs in PC dogs, is the direct consequence of an enhanced nitric oxide 7 synthase (NOS) activity or other NO producing mechanisms, such as the non-enzymatic NO formation, may also play a role. Therefore, we designed studies in which the time-course changes in NOS activity, NO bioavailability, as well as superoxide and NT productions were simultaneously examined in control dogs and in dogs subjected to PC. We have found that in control dogs subjected to a 25 min LAD occlusion, there was an initial increase in NOS activation that occurred around 5 min of the occlusion. Afterwards the enzyme activity continuously decreased up to the end of the occlusion period. These changes in NOS activity were almost parallel with the alterations in NO levels. In control dogs, there were also marked increases in tissue superoxide and NT concentrations, determined at the end of the 25 min of the occlusion. In contrast, in dogs subjected to PC the activation of NOS and the production of NO were significantly increased during the PC procedure, and these were maintained over the entire period of the subsequent prolonged ischaemic insult. Although the P...

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Early preconditioning prevents the loss of endothelial nitric oxide synthase and enhances its activity in the ischemic/reperfused rat heart

Cited by 25 publications

References 37 publications

Ischemic Preconditioning Attenuates Postischemic Leukocyte - Endothelial Cell Interactions Role of Nitric Oxide and Protein Kinase C

Ischemic Preconditioning Attenuates Postischemic Leukocyte - Endothelial Cell Interactions Role of Nitric Oxide and Protein Kinase C

Endothelial Nitric Oxide Contributes to the Renal Protective Effects of Ischemic Preconditioning

Further evidence for the role of nitric oxide in the antiarrhythmic effect of ischaemic preconditioning: the effect of peroxynitrite and changes in NOS-dependent NO production

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