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

Jun Su, Shengjun Zhang, James Tse, Peter M. Scholz, Harvey R. Weiss

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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-Lepob) 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.

Original languageEnglish (US)
Pages (from-to)H2111-H2117
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume285
Issue number5 54-5
DOIs
StatePublished - Nov 2003

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Physiology

Keywords

  • Myocyte shortening
  • Protein kinase
  • Soluble guanylyl cyclase

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