Alterations in nitric oxide-cGMP pathway in ventricular myocytes from obese leptin-deficient mice
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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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
- Publisher
- American Physiological Society
- 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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