Sarcolemmal Na+-Ca2+ exchange activity in hearts subjected to hypoxia reoxygenation

Dixon, Ian M.C.; Eyolfson, Douglas A.; Dhalla, Naranjan S.

doi:10.1152/ajpheart.1987.253.5.h1026

Cited by 32 publications

(16 citation statements)

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“…The mechanism underlying the increase in NO production is not known. An increase in [Ca 2+ ] i under hypoxic conditions (Dixon et al 1987;Zhu and Nosek 1991) may serve as a second messenger to active NOS (Hampl et al 1995). Increases in NOS in pulmonary artery endothelium during hypoxia [4.9 kPa (about 38 mmHg)] were triggered by the initial transient increase in [Ca 2+ ] i (Hampl et al 1995).…”

Section: Effects Of No On Force Generation During Hypoxiamentioning

confidence: 99%

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Role of nitric oxide in isometric contraction properties of rat diaphragm during hypoxia

et al. 2003

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Hypoxia disturbs Ca(2+) regulation and increases the intracellular Ca(2+) concentration ([Ca(2+)](i)), which may in turn activate the nitric oxide synthase (NOS) regulated by [Ca(2+)](i). Since nitric oxide (NO) reduces the isometric contractility of rat diaphragm in vitro, we hypothesized that NO contributes to the impaired force generation of an hypoxic diaphragm. The effects of different concentrations of the NOS inhibitor, N(G)-monomethyl-L-arginine (L-NMMA), the NO scavenger haemoglobin (150 micro mol.l(-1)) and the NO donor spermine NONOate (Sp-NO; 1 mmol.l(-1)) were determined on isometric contractility during hypoxia [partial pressure of oxygen, PO(2), about 7 kPa (about 54 mmHg)] and hyperoxia [ PO(2) about 83 kPa (about 639 mmHg)]. Hypoxia significantly reduced maximal twitch force ( F(t)), and submaximal tetanic force (30 Hz, F(30)) in all L-NMMA groups. A low concentration of L-NMMA (30 micromol.l(-1)) increased F(30) but a high concentration (1,000 micromol.l(-1)) reduced F(30) during hypoxia. The effects of L-NMMA on force generation were more pronounced during hypoxia compared to hyperoxia. Peak increases in F(30) and F(t) were observed at a concentration of 30 micromol.l(-1) L-NMMA during hypoxia, but with 10 micromol.l(-1) L-NMMA during hyperoxia. The same concentration of haemoglobin increased F(30) and F(t) less during hypoxia compared to hyperoxia. The Sp-NO reduced F(t), F(30) and maximal tetanic force (F(0)) during hypoxia; these effects were abolished in the presence of haemoglobin. The Sp-NO did not alter F(t), F(30) and F(0)during hyperoxia. We conclude that NO plays a more prominent role during hypoxia and that NO contributes to the depression of force generation in the hypoxic rat diaphragm in vitro. This change may be related to an elevated NO generation within the hypoxic diaphragm.

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Section: Effects Of No On Force Generation During Hypoxiamentioning

confidence: 99%

“…Hypoxia has been found to impair the re-uptake of Ca 2+ by the sarcoplasmic reticulum (SR) from the intracellular space (Dixon et al 1987;Zhu and Nosek 1991). This could result in an increase of intracellular Ca 2+ concentrations ([Ca 2+ ] i ), which, in turn, may potentiate NO production (Hampl et al 1995).…”

Section: Introductionmentioning

confidence: 99%

Role of nitric oxide in isometric contraction properties of rat diaphragm during hypoxia

et al. 2003

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“…It is also possible that hypoxia directly affects NOS. Previous studies showed that hypoxia impairs the SR Ca 2ϩ reuptake from the intracellular space (12,52). This could result in an increase of [Ca 2ϩ ] i levels (52) and may, in turn, activate NOS via Ca 2ϩ -dependent NOS isoforms.…”

Section: Effects Of No On Isotonic Contractile and Fatigue Propertiesmentioning

confidence: 99%

“…Furthermore, the isotonic contractile properties better reflect diaphragm muscle performance in vivo (46). Hypoxia impairs the sarcoplasmic reticulum (SR) Ca 2ϩ reuptake from the intracellular space (12,52). This could result in an increase of intracellular Ca 2ϩ concentration levels ([Ca 2ϩ ] i ) and may, in turn, potentiate NO production by Ca 2ϩ -dependent NOS (19).…”

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confidence: 99%

Effects of modulation of nitric oxide on rat diaphragm isotonic contractility during hypoxia

Zhu

Heunks

Machiels

et al. 2003

Journal of Applied Physiology

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Effects of modulation of nitric oxide on rat diaphragm isotonic contractility during hypoxia. J Appl Physiol 94: 612-620, 2003. First published October 18, 2002 10.1152/ japplphysiol.00441.2002 is essential for optimal myofilament function of the rat diaphragm in vitro during active shortening. Little is known about the role of NO in muscle contraction under hypoxic conditions. Hypoxia might increase the NO synthase (NOS) activity within the rat diaphragm. We hypothesized that NO plays a protective role in isotonic contractile and fatigue properties during hypoxia in vitro. The effects of the NOS inhibitor N G -monomethyl-L-arginine (L-NMMA), the NO scavenger hemoglobin, and the NO donor spermine NONOate on shortening velocity, power generation, and isotonic fatigability during hypoxia were evaluated (PO 2 ϳ 7 kPa). L-NMMA and hemoglobin slowed the shortening velocity, depressed power generation, and increased isotonic fatigability during hypoxia. The effects of L-NMMA were prevented by coadministration with the NOS substrate L-arginine. Spermine NONOate did not alter isotonic contractile and fatigue properties during hypoxia. These results indicate that endogenous NO is needed for optimal muscle contraction of the rat diaphragm in vitro during hypoxia.N G -monomethyl-L-arginine; hemoglobin; spermine NONOate SKELETAL MUSCLE, INCLUDING the diaphragm, continuously produces nitric oxide (NO) (3,26). NO is produced in biological systems via the enzymatic action of NO synthase (NOS) (32). NO generation by the constitutive NOS isoforms (neuronal NOS and endothelial NOS) is calcium dependent (16). NO production within skeletal muscle is enhanced during contractile activity (5).NO has been shown to modulate contractile properties of skeletal muscle in vitro. The overall effect depends on the experimental paradigm. Inhibition of NOS increases twitch and submaximal tetanic force of the rat diaphragm. These alterations are reversed by NO donors (26), suggesting that NO inhibits excitation-contraction coupling in unfatigued muscle. On the other hand, NO is essential for optimal myofilament function in the rat diaphragm during active shortening in vitro (36). Inhibition of NOS decreases the shortening velocity and power generation of the rat diaphragm under hyperoxic conditions (36). These findings of NOS inhibition on force generation and velocity of shortening indicate multiple possible targets for NO in skeletal muscle. In fatiguing contractions, supplementation with exogenous NO slowed the decline of maximal force in mouse soleus muscle (38). This finding suggests that NO preserves skeletal muscle function in vitro during strenuous contractile activity.Hypoxia impairs force generation and accelerates skeletal muscle fatigue in vitro (21, 48). To date, no study has investigated the role of NO in shortening velocity or isotonic fatigability during hypoxia. This is of particular interest because NO affects excitationcontraction coupling in striated muscle (26), and O 2 tension is an important factor in regulating NOS in an...

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“…Furthermore, Hata et al [84] showed that various types of oxygen free radical-generating systems inhibited the Na+-Ca 2+ exchange activity in sarcolemmal membrane vesicles isolated from rat, bovine, canine, and porcine hearts. Bersohn et al [ I 12], Daly et al [ 109], Meon et al [110], and Dixon et al [111,113] reported that heart sarcolemmal Na+-Ca 2 § exchange activity was depressed in hearts subjected to ischemia-reperfusion or hypoxiareoxygenation, and that the reduced activity of Na+-Ca 2+ exchange in ischemia-reperfused hearts was prevented by the addition of free radical scavengers to the perfusate [ 113].…”

Section: Na+-ca 2+ Exchangementioning

confidence: 99%

Oxygen free radicals and calcium homeostasis in the heart

et al. 1994

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Many experiments have been done to clarify the effects of oxygen free radicals on Ca 2+ homeostasis in the hearts. A burst of oxygen free radicals occurs immediately after reperfusion, but we have to be reminded that the exact levels of oxygen free radicals in the hearts are yet unknown in both physiological and pathophysiological conditions. Therefore, we should give careful consideration to this point when we perform the experiments and analyze the results.It is, however, evident that Ca 2+ overload occurs when the hearts are exposed to an excess amount of oxygen free radicals. Though ATP-independent Ca 2+ binding is increased, Ca 2+ influx through Ca 2 § channel does not increase in the presence of oxygen free radicals. Another possible pathway through which Ca 2. can enter the myocytes is Na+-Ca 2+ exchanger. Although, the activities ofNa § + ATPase and Na+-H + exchange are inhibited by oxygen free radicals, it is not known whether intracellular Na § level increases under oxidative stress or not. The question has to be solved for the understanding of the importance of Na § Ca z+ exchange in Ca 2+ influx process from extracellular space. Another question is 'which way does Na+-Ca 2+ exchange work under oxidative stress? Net influx or efflux of Ca 2 § ?' Membrane permeability for Ca 2+ may be maintained in a relatively early phase of free radical injury. Since sarcolemmal Ca2+-pumpATPase activity is depressed by oxygen free radicals, Ca 2 § extrusion from cytosol to extracellular space is considered to be reduced. It has also been shown that oxygen free radicals promote Ca 2 § release from sarcoplasmic reticulum and inhibit Ca 2+ sequestration to sarcoplasmic reticulum. Thus, these changes in Ca 2+ handling systems could cause the Ca 2+ overload due to oxygen free radicals. (Mol Cell Biochem 139: 91-100, 1994)

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Sarcolemmal Na+-Ca2+ exchange activity in hearts subjected to hypoxia reoxygenation

Cited by 32 publications

References 0 publications

Role of nitric oxide in isometric contraction properties of rat diaphragm during hypoxia

Role of nitric oxide in isometric contraction properties of rat diaphragm during hypoxia

Effects of modulation of nitric oxide on rat diaphragm isotonic contractility during hypoxia

Oxygen free radicals and calcium homeostasis in the heart

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