Chronic NG-nitro-L-argininr methyl ester (L-name) administration in C57BL/6J mice induces a sustained decrease in c-kit positive cells during development of cardiac hypertrophy

R. J. Ocsan, Y. N. Lai, K. V. Prabhu, B. D. Hambly, C. S. McLachlan

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8 Citations (Scopus)

Abstract

Chronic NG-nitro-l-arginine methyl ester (L-NAME) administration induces cardiac hypertrophy in rodent models. Our aims is to determine the role of c-kit expression in L-NAME induced cardiac hypertrophy. 12-20 week old C57BL/6J mice (5 per group) were administered L-NAME (0.325mg/ml) in the drinking water. Hearts were excised at 1-day, 2-days, 5-days, 2-weeks or 6-weeks; or controls which received no L-NAME. Ventricular cross-sectional wall thickness and individual cardiac myocytes cross-sectional area and cardiomyocyte/nuclear ratio to determine cardiac hypertrophy. Immuno-histochemical staining for c-kit, sca-1 and BCRP undertaken. Six weeks L-NAME administration induced significant cardiac hypertrophy compared to control hearts, evidenced by an increase in the thickness of the cross-sectional free ventricular wall (p<0.05) and an increase in mean individual cross-sectional area of cardiac myocytes in the LV wall (p<0.007). We observed c-kit+ cells (predominately non-mast cell sub-types) in both healthy mice and in the L-NAME treated mice. C-kit staining in the left ventricular cross sections following L-NAME remained stable at 1 and 2 days compared to controls (p=NS). After 5 days of L-NAME we observed c-kit expression to decrease below control levels (p<0.05) and these lower levels were sustained at 2 and 6 weeks. C-kit expression does not decrease during two days of L-NAME administration, suggesting, firstly, that the later decrease in c-kit is not due to NOS inhibition directly and, secondly, there is the possibility for c-kit+ cell differentiation into other cell types, possibly inducing myocardial cellular hyperplasia, without significant replacement of the original pool of c-kit+ cells.

Original languageEnglish
JournalJournal of Physiology and Pharmacology
Volume64
Issue number6
Publication statusPublished - 1 Jan 2013
Externally publishedYes

Keywords

  • c-kit
  • Cardiac hypertrophy
  • Cardiac myocyte
  • NG-nitro-L-arginine methyl ester
  • Nitric oxide synthase
  • Non-mast cells

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