Cited by 12Cardiovascular Function and Risk FactorsNitric Oxide and Endothelin EffectsPhosphodiesterase function and regulation

Alterations in nitric oxide-cGMP pathway in ventricular myocytes from obese leptin-deficient mice

Su, Jun, Zhang, Shengjun, Tse, James, Scholz, Peter M., Weiss, Harvey R.·2003·American Journal of Physiology-Heart and Circulatory Physiology

Abstract

Leptin is a regulator of body weight and affects nitric oxide (NO) production. This study was designed to determine whether the myocardial NO-cGMP signal transduction system was altered in leptin-deficient obese mice. Contractile function, guanylyl cyclase activity, and cGMP-dependent protein phosphorylation were assessed in ventricular myocytes isolated from genetically obese (B6.V-Lep ob) and age-matched lean (C57BL/6J) mice. There were no differences in baseline contraction between the lean and obese groups. After stimulation with the NO donor S-nitroso- N-acetyl-penicillamine (SNAP, 10–6 and 10–5 M) or a membrane-permeable cGMP analog 8-bromo-cGMP (8-Br-cGMP, 10–6 and 10–5 M), cell contractility was depressed. However, 8-Br-cGMP had significantly greater effects in obese mice than in lean controls with percent shortening reduced by 47 vs. 39% and maximal rate of shortening decreased by 46 vs. 36%. The negative effects of SNAP were similar between the two groups. Soluble guanylyl cyclase activity was not attenuated. This suggests that the activity of the cGMP-independent NO pathway may be enhanced in obesity. The phosphorylated protein profile of cGMP-dependent protein kinase showed that four proteins were more intensively phosphorylated in obese mice, which suggests an explanation for the enhanced effect of cGMP. These results indicate that the NO-cGMP signaling pathway was significantly altered in ventricular myocytes from the leptin-deficient obese mouse model.

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Crossref · 10.1152/ajpheart.00316.2003

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  • Ob/ob cardiomyocytes are more susceptible to nitric oxide (NO)-mediated depression in contractility relative to nonobese controls.

    “Ob/ob cardiomyocytes are also more susceptible to nitric oxide (NO)-mediated depression in contractility relative to nonobese controls (330).”

    From Cardiac remodeling in obesity (2008) · cites this paper as [330]

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Authors
Su, J., Zhang, S., Tse, J., Scholz, P. M., & Weiss, H. R.
Affiliations
University of Medicine and Dentistry of New Jersey (US)
Venue
American Journal of Physiology-Heart and Circulatory Physiology
Published
2003-11
Volume
285
Issue
5
Pages
H2111-H2117
ISSN
  • 0363-6135 (ISSN-L)
  • 1522-1539
OpenAlex
W2108297957
Cited by
12
References
34
FWCI
1.54
Type
journal article
Language
en
Open access
closed
Locations
  • American Journal of Physiology-Heart and Circulatory Physiology (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Heart, Lung, and Blood Institute (HL-40320)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Phosphodiesterase function and regulation
Keywords
nitric oxide, cGMP signaling, leptin deficiency, obesity, ventricular myocytes, soluble guanylate cyclase, cGMP-dependent protein kinase, protein phosphorylation, cardiac contractility, 8-bromo-cGMP, SNAP
MeSH terms
Animals, Cyclic GMP, Heart Ventricles, Mice, Inbred C57BL, Mice, Obese, Myocardial Contraction, Nitric Oxide, Obesity, Penicillamine, Nitric Oxide Donors, Leptin, Myocytes, Cardiac, Mice

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