Effects of the Nitric Oxide Donor Sodium Nitroprusside on Intracellular pH and Contraction in Hypertrophied Myocytes

Ito, Nobuhiko; Bartunek, J.; Spitzer, Kenneth W.; Lorell, Beverly H.

doi:10.1161/01.cir.95.9.2303

Cited by 74 publications

(60 citation statements)

References 39 publications

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“…It also has been well demonstrated that E2 increases activity of NOS and NO release during ischemia and reperfusion (20,39,41). Furthermore, there is good evidence that the NO donor sodium nitroprusside, as well as 8-bromoguanosine 3Ј,5Ј-cyclic monophosphate (8-BrcGMP), inhibit pH i recovery in cardiac myocytes from male rats after NH 4 Cl washout in HEPES medium (22). The latter supports the conclusion that NO (via cGMP) inhibits pHregulatory NHE in the heart.…”

Section: Discussionmentioning

confidence: 98%

“…Therefore, we tested the hypothesis that E2 will inhibit NHE1 under normoxic, normal flow conditions of intracellular acidification using the NH 4 Cl prepulse technique under HEPES-buffered conditions (8,22). Under these conditions, a known amount or bolus of protons can be "injected" into the cell, and the rate of proton efflux during pH i recovery can be ascribed to flux via Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Given the aforementioned evidence that E2 stimulates release of NO and that NO inhibits NHE1 in cardiac myocytes (22), we tested the hypothesis that acute exposure of isolated rat hearts to E2 limits Na ϩ uptake during ischemia-reperfusion and thus limit Na ϩ -dependent increases in [Ca 2ϩ ] i as well as associated ischemia-reperfusion injury. The hypothesis further predicts that this effect of E2 is inhibited by the NO synthesis inhibitor N -nitro-L-arginine methyl ester (L-NAME).…”

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confidence: 99%

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Acute effects of 17β-estradiol on myocardial pH, Na⁺, and Ca²⁺ and ischemia-reperfusion injury

Anderson¹,

Kirkland²,

Beyschau³

et al. 2005

American Journal of Physiology-Cell Physiology

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Evidence suggests that 1) ischemia-reperfusion injury is due largely to cytosolic Ca 2ϩ accumulation resulting from functional coupling of Na ϩ /Ca 2ϩ exchange (NCE) with stimulated Na ϩ /H ϩ exchange (NHE1) and 2) 17␤-estradiol (E2) stimulates release of NO, which inhibits NHE1. Thus we tested the hypothesis that acute E2 limits myocardial Na ϩ and therefore Ca 2ϩ accumulation, thereby limiting ischemia-reperfusion injury. NMR was used to measure cytosolic pH (pHi), Na ϩ (Na i ϩ ), and calcium concentration ([Ca 2ϩ ]i) in Krebs-Henseleit (KH)-perfused hearts from ovariectomized rats (OVX). Left ventricular developed pressure (LVDP) and lactate dehydrogenase (LDH) release were also measured. Control ischemia-reperfusion was 20 min of baseline perfusion, 40 min of global ischemia, and 40 min of reperfusion. The E2 protocol was identical, except that 1 nM E2 was included in the perfusate before ischemia and during reperfusion. E2 significantly limited the changes in pH i, Na i ϩ , and [Ca 2ϩ ]i during ischemia (P Ͻ 0.05). In control OVX vs. OVXϩE2, pH i fell from 6.93 Ϯ 0.03 to 5.98 Ϯ 0.04 vs. 6.96 Ϯ 0.04 to 6.68 Ϯ 0.07; Na i ϩ rose from 25 Ϯ 6 to 109 Ϯ 14 meq/kg dry wt vs. 25 Ϯ 1 to 76 Ϯ 3; [Ca 2ϩ ]i changed from 365 Ϯ 69 to 1,248 Ϯ 180 nM vs. 293 Ϯ 66 to 202 Ϯ 64 nM. E2 also improved recovery of LVDP and diminished release of LDH during reperfusion. Effects of E2 were diminished by 1 M N -nitro-L-arginine methyl ester. Thus the data are consistent with the hypothesis. However, E2 limitation of increases in [Ca 2ϩ ]i is greater than can be accounted for by the thermodynamic effect of reduced Na i ϩ accumulation on NCE. myocardial ischemia; Na ϩ /H ϩ exchange; Na ϩ /Ca 2ϩ exchange; nuclear magnetic resonance; ischemic biology; ion channels/membrane transport; transplantation IT IS CLEAR THAT OUR UNDERSTANDING of the effects of endogenous and exogenous estrogen on the cardiovascular system, and in particular on its role in modifying susceptibility to ischemic injury, is deficient. It is more important than ever that fundamental research be conducted to understand the basis for the effects of estrogen (50). Because results of various studies are inconsistent and/or difficult to interpret, we have taken a reductionist approach to testing the acute effects of exogenous 17␤-estradiol (E2) on ischemic myocardium within the context of the well-accepted paradigm that ischemic injury is largely the result of the following chain of events. Anaerobic metabolism decreases cytosolic pH (pH i ), which stimulates pHregulatory Na ϩ /H ϩ exchange (NHE1) to increase Na ϩ uptake and thereby increase intracellular Na ϩ (Na i ϩ ). Increases in (3,7,31,37,46,49). In the heart, there are questions about whether the bulk of Na ϩ and Ca 2ϩ entry occurs during ischemia or reperfusion, but there is a growing consensus that much of the Ca 2ϩ entry is Na ϩ dependent (36). Numerous studies have shown that E2 stimulates NOS activity and/or the release of nitric oxide (NO) in the heart (20,39,40) and that female hormonelinked changes in Na ϩ...

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Acute effects of 17β-estradiol on myocardial pH, Na⁺, and Ca²⁺ and ischemia-reperfusion injury

Anderson¹,

Kirkland²,

Beyschau³

et al. 2005

American Journal of Physiology-Cell Physiology

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“…Reactive oxygen species also may lead to the induction of acidosis-induced cellular toxicity and subsequent mitochondrial failure (Chong, et al, 2005f). Disorders, such as hypoxia (Roberts and Chih, 1997), diabetes (Cardella, 2005, Kratzsch, et al, 2006, and excessive free radical production (Ito, et al, 1997 can result in the disturbance of intracellular pH.…”

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confidence: 99%

Erythropoietin and Oxidative Stress

Maiese

Chong

Hou

et al. 2008

CNR

108

113

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Unmitigated oxidative stress can lead to diminished cellular longevity, accelerated aging, and accumulated toxic effects for an organism. Current investigations further suggest the significant disadvantages that can occur with cellular oxidative stress that can lead to clinical disability in a number of disorders, such as myocardial infarction, dementia, stroke, and diabetes. New therapeutic strategies are therefore sought that can be directed toward ameliorating the toxic effects of oxidative stress. Here we discuss the exciting potential of the growth factor and cytokine erythropoietin for the treatment of diseases such as cardiac ischemia, vascular injury, neurodegeneration, and diabetes through the modulation of cellular oxidative stress. Erythropoietin controls a variety of signal transduction pathways during oxidative stress that can involve Janus-tyrosine kinase 2, protein kinase B, signal transducer and activator of transcription pathways, Wnt proteins, mammalian forkhead transcription factors, caspases, and nuclear factor κB. Yet, the biological effects of erythropoietin may not always be beneficial and may be poor tolerated in a number of clinical scenarios, necessitating further basic and clinical investigations that emphasize the elucidation of the signal transduction pathways controlled by erythropoietin to direct both successful and safe clinical care. KeywordsAlzheimer's disease; Akt; angiogenesis; apoptosis; cancer; cardiac; caspases; diabetes; endothelial; erythropoietin; forkhead; FoxO; GSK-3β; inflammation; mitochondria; NF-κB; renal; STATs; Wnt OXIDATIVE STRESSInitial work in pathways that can lead to oxidative stress by early investigators observed that increased metabolic rates could be detrimental to animals in an elevated oxygen environment. More current studies point to the potential aging mechanisms and accumulated toxic effects for an organism that are tied to oxidative stress (Maiese, et al., 2008a NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript in organisms, or at least the rate of oxygen consumption in organisms, has intrigued several investigators. Pearl proposed that increased exposure to oxygen through an increased metabolic rate could lead to a shortened life span (Pearl, 1928). Subsequent work by multiple investigators has furthered this hypothesis by demonstrating that increased metabolic rates could be detrimental to animals in an elevated oxygen environment . When one moves to more current work, oxygen free radicals and mitochondrial DNA mutations have become associated with oxidative stress injury, aging mechanisms, and accumulated toxicity for an organism (Yui and Matsuura, 2006).Oxygen free radicals can be generated in elevated quantities during the reduction of oxygen and subsequently lead to cell injury and apoptosis. Oxidative stress occurs as a result of the development of reactive oxygen species that consist of oxygen free radicals and other chemical entities. These agents can involve superoxide free radicals, hydrogen peroxide, sin...

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“…5,6 In isolated rat ventricular myocytes, both 8-bromo-cGMP and SNP induced earlier isotonic twitch relaxation and an increase in diastolic cell length, which were not accompanied by changes in cytosolic Ca 2ϩ transients and were therefore attributed to a reduction in myofilament responsiveness to Ca 2ϩ . 7,8 In isolated ejecting guinea pig hearts, either SNP, substance P, or bradykinin induced NO-dependent enhancement of LV relaxation without altering the maximal rate of LV pressure rise (LV dP/dt max ). 9,10 In human subjects with normal LV function undergoing diagnostic cardiac catheterization, bicoronary infusion of SNP or substance P induced earlier onset of LV relaxation without changes in LV dP/dt max .…”

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confidence: 99%

Impaired Endothelium-Dependent Regulation of Ventricular Relaxation in Pressure-Overload Cardiac Hypertrophy

MacCarthy

Shah

2000

Circulation

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Background-Endothelium-derived nitric oxide (NO) selectively enhances myocardial relaxation and may benefit diastolic function. Left ventricular hypertrophy (LVH) is characterized by abnormal myocardial relaxation and endothelial dysfunction. We investigated endothelium-dependent regulation of LV relaxation in moderate pressureoverload LVH induced by aortic banding in guinea pigs. Methods and Results-Isolated ejecting hearts of banded or sham-operated animals (shams) were studied. The specific agonists for endothelial release of NO, bradykinin (10 nmol/L), and substance P (100 nmol/L) both induced earlier onset of LV relaxation in shams (time to LV dP/dt min [tdP/dt min ], Ϫ13.4Ϯ3.0 and Ϫ10.4Ϯ2.5 ms, respectively) without altering peak LV pressure or LV dP/dt max . Neither agent altered tdP/dt min in banded animals. The ACE inhibitor captopril (1 mol/L) also selectively reduced tdP/dt min in shams via a bradykinin/NO-dependent mechanism but had no effect in banded animals. An exogenous NO donor, sodium nitroprusside (0.1 mol/L), selectively reduced tdP/dt min to a similar extent in both shams and banded animals. Endothelial-type NO synthase (eNOS) protein expression in whole LV homogenate was unaltered in banded animals. Conclusions-Endothelium-dependent enhancement of LV relaxation is impaired in moderate pressure-overload LVH, despite a preserved response to exogenous NO. This is not accounted for by altered eNOS expression. These abnormalities may contribute to diastolic dysfunction in

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Effects of the Nitric Oxide Donor Sodium Nitroprusside on Intracellular pH and Contraction in Hypertrophied Myocytes

Abstract: SNP and 8-bromo-cGMP cause a negative inotropic effect and depress the rate of recovery from intracellular acidification that is mediated by Na(+)-H+ exchange in normal adult rat myocytes. In contrast, SNP and 8-bromo-cGMP do not modify cell contraction or pHi in hypertrophied myocytes.

Cited by 74 publications

References 39 publications

Acute effects of 17β-estradiol on myocardial pH, Na⁺, and Ca²⁺ and ischemia-reperfusion injury

Acute effects of 17β-estradiol on myocardial pH, Na⁺, and Ca²⁺ and ischemia-reperfusion injury

Erythropoietin and Oxidative Stress

Impaired Endothelium-Dependent Regulation of Ventricular Relaxation in Pressure-Overload Cardiac Hypertrophy

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Effects of the Nitric Oxide Donor Sodium Nitroprusside on Intracellular pH and Contraction in Hypertrophied Myocytes

Abstract: SNP and 8-bromo-cGMP cause a negative inotropic effect and depress the rate of recovery from intracellular acidification that is mediated by Na(+)-H+ exchange in normal adult rat myocytes. In contrast, SNP and 8-bromo-cGMP do not modify cell contraction or pHi in hypertrophied myocytes.

Cited by 74 publications

References 39 publications

Acute effects of 17β-estradiol on myocardial pH, Na+, and Ca2+ and ischemia-reperfusion injury

Acute effects of 17β-estradiol on myocardial pH, Na+, and Ca2+ and ischemia-reperfusion injury

Erythropoietin and Oxidative Stress

Impaired Endothelium-Dependent Regulation of Ventricular Relaxation in Pressure-Overload Cardiac Hypertrophy

Contact Info

Product

Resources

About

Acute effects of 17β-estradiol on myocardial pH, Na⁺, and Ca²⁺ and ischemia-reperfusion injury

Acute effects of 17β-estradiol on myocardial pH, Na⁺, and Ca²⁺ and ischemia-reperfusion injury