Nitric oxide attenuates cardiac myocyte contraction

Brady, Adrian; Warren, J. B.; Poole-Wilson, P. A.; Williams, Taffy J.; Harding, Siân E.

doi:10.1152/ajpheart.1993.265.1.h176

Cited by 224 publications

(192 citation statements)

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“…Both 'A' flow velocity integ 'A' velocity remained constant throug result strong trends were seen to both de flow velocity integral ratio, and peak E/A [20]. The lack of associated changes in cardiac dimensions is not, altogether -ardiac index surprising since M-mode echocardiography is only a 10.5 mg kg-' 1-dimensional measurement of a 3-dimensional strucit changes in ture, and therefore any volume changes would have Although a to be large to be detectable with accuracy on the M-11 stress was mode recordings.…”

Section: Systolic and Diastolic Function (Tables 3 Figures 2 3 And 4)mentioning

confidence: 81%

Influence of basal nitric oxide secretion on cardiac function in man.

Clarkson

Lim

MacDonald

1995

Brit J Clinical Pharma

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1 Nitric oxide is recognised as an important biological mediator, which is thought to be involved in cardiovascular homeostasis. placebo. 3 A trend towards reduction in heart rate was observed with L-NMMA infusion although this did not reach statistical significance, whereas significant increases in both systolic blood pressure (at 2.0 mg kg-' h-1) and systemic vascular resistance index (at 0.5 mg kg-' h-1) were seen.4 L-NMMA infusion caused significant reductions in stroke distance and cardiac index, although there was no change in the ratio of end systolic wall stress/end systolic volume index (an afterload independent index of left ventricular systolic performance). 5 The isovolumic relaxation time significantly increased with L-NMMA infusion, together with a significant reduction in the 'E' wave flow velocity integral. Reductions in both peak E/A ratio and E/A flow velocity integral ratio were also seen, although these failed to reach statistical significance. 6 In conclusion, the basal generation of nitric oxide in man appears to maintain a vasodilated state, and modifies left ventricular diastolic filling parameters.

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Section: Systolic and Diastolic Function (Tables 3 Figures 2 3 And 4)mentioning

confidence: 81%

Influence of basal nitric oxide secretion on cardiac function in man.

Clarkson

Lim

MacDonald

1995

Brit J Clinical Pharma

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“…On the other hand, negative inotropic e ects of SNP have been reported in the literature (e.g. Smith et al, 1991;Brady et al, 1993), although these are generally of small magnitude compared to the responses commonly observed with muscarinic agonists. The reasons for the discrepancies in the published reports are not clear at the present time.…”

Section: Discussionmentioning

confidence: 96%

Cyclic GMP‐dependent protein kinase activation in the absence of negative inotropic effects in the rat ventricle

MacDonell

Diamond

1997

British J Pharmacology

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1 It has been suggested that activation of cyclic GMP-dependent protein kinase (PKG) is a necessary step in the chain of events leading to the production of negative inotropy by muscarinic receptor agonists in mammalian ventricles, and that some cyclic GMP-elevating agents, such as sodium nitroprusside (SNP), fail to exert a negative inotropic e ect because they elevate cyclic GMP levels in a pool that does not activate the kinase. This hypothesis was tested in the present study by monitoring the e ects of carbachol, SNP and atrial natriuretic peptide (ANP) on contractility, cyclic GMP content and PKG activity in rat intact ventricular preparations and freshly isolated ventricular cardiomyocytes. 2 The presence of PKG in both the intact vehicle and in isolated ventricular cardiomyocytes was con®rmed by MonoQ anion exchange chromatography and Western blotting. The elution pro®le indicated that the conditions of the PKG assay were selective for measuring PKG activity. 3 Carbachol induced a marked negative inotropic e ect in intact, perfused hearts and ventricular strips in the presence of isoproterenol. The negative inotropic e ect of carbachol was not associated with signi®cant changes in cyclic GMP content or PKG activity in intact ventricular tissue, or in PKG activity in isolated cardiomyocytes. 4 SNP and ANP signi®cantly increased cyclic GMP levels and activated PKG in intact ventricular preparations. Both drugs also activated PKG in isolated cardiomyocytes. However, neither drug had any negative inotropic e ect in isoprenaline-stimulated perfused hearts and ANP did not change the contractility of isoprenaline-stimulated isolated cardiomyocytes. 5 The results of this study demonstrate that the negative inotropic e ects of muscarinic receptor agonists can occur in the absence of signi®cant activation of PKG. Conversely, marked increases in ventricular cyclic GMP content and PKG activity caused by SNP or ANP were not accompanied by a negative inotropic e ect. 6 These results suggest that increases in cyclic GMP levels and activation of PKG do not play important roles in the regulation of rat ventricular contractility by muscarinic receptor agonists.

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“…As a proinflammatory cytokine, it induces the expression of IL-1␤, tumor necrosis factor-␣, and iNOS (14,15). Both IL-1␤ and tumor necrosis factor-␣ act as negative myocardial inotropes, and induction of iNOS and iNOS-mediated nitric oxide generation play a critical role in myocardial dysfunction (57)(58)(59)(60)(61)(62). Recently, administration of IL-18 has been shown to induce myocardial contractile function in vivo and cardiomyocyte contractility in vitro (18), suggesting that IL-18 may play a role in post-ischemic myocardial dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-18 Is a Pro-hypertrophic Cytokine That Acts through a Phosphatidylinositol 3-Kinase-Phosphoinositide-dependent Kinase-1-Akt-GATA4 Signaling Pathway in Cardiomyocytes

Chandrasekar

Mummidi

Claycomb

et al. 2005

Journal of Biological Chemistry

116

113

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In patients with congestive heart failure, high serum levels of the proinflammatory cytokine interleukin (IL)-18 were reported. A positive correlation was described between serum IL-18 levels and the disease severity. IL-18 has also been shown to induce atrial natriuretic factor (ANF) gene expression in adult cardiomyocytes. Because re-expression of the fetal gene ANF is mostly associated with hypertrophy, a hallmark of heart failure, we hypothesized that IL-18 induces cardiomyocyte hypertrophy. Treatment of the cardiomyocyte cell line HL-1 with IL-18 induced hypertrophy as characterized by increases in protein synthesis, phosphorylated p70 S6 kinase, and ribosomal S6 protein levels as well as cell surface area. Furthermore, IL-18 induced ANF gene transcription in a time-dependent manner as evidenced by increased ANF secretion and ANF promoter-driven reporter gene activity. Investigation into possible signal transduction pathways mediating IL-18 effects revealed that IL-18 activates phosphoinositide 3-kinase (PI3K), an effect that was blocked by wortmannin and LY-294002. IL-18 induced Akt phosphorylation and stimulated its activity, effects that were abolished by Akt inhibitor or knockdown. IL-18 stimulated GATA4 DNA binding activity and increased transcription of a reporter gene driven by multimerized GATA4-binding DNA elements. Pharmacological inhibition or knockdown studies revealed that IL-18 induced cardiomyocyte hypertrophy and ANF gene transcription via PI3K, PDK1, Akt, and GATA4. Most importantly, IL-18 induced ANF gene transcription and hypertrophy of neonatal rat ventricular myocytes via PI3K-, Akt-, and GATA4-dependent signaling. Together these data provide the first evidence that IL-18 induces cardiomyocyte hypertrophy via PI3K-dependent signaling, defines a mechanism of IL-18-mediated ANF gene transcription, and further supports a role for IL-18 in inflammatory heart diseases including heart failure.

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Nitric oxide attenuates cardiac myocyte contraction

Cited by 224 publications

References 0 publications

Influence of basal nitric oxide secretion on cardiac function in man.

Influence of basal nitric oxide secretion on cardiac function in man.

Cyclic GMP‐dependent protein kinase activation in the absence of negative inotropic effects in the rat ventricle

Interleukin-18 Is a Pro-hypertrophic Cytokine That Acts through a Phosphatidylinositol 3-Kinase-Phosphoinositide-dependent Kinase-1-Akt-GATA4 Signaling Pathway in Cardiomyocytes

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