title: Chronic NG-nitro-l-arginine methyl ester (L-NAME) administration in C57BL/6J mice induces a sustained decrease in c-kit positive cells during development of cardiac hypertrophy.
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.
authors.affiliation: Discipline of Pathology, Sydney Medical School, University of Sydney, Sydney, Australia. reperfusion@hotmail.com.
authors.forename: R J
authors.initials: RJ
authors.lastname: Ocsan
authors.forename: Y N
authors.initials: YN
authors.lastname: Lai
authors.forename: K V
authors.initials: KV
authors.lastname: Prabhu
authors.forename: B D
authors.initials: BD
authors.lastname: Hambly
authors.forename: C S
authors.initials: CS
authors.lastname: McLachlan
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D006352:Heart Ventricles / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*
chemical_list: D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D019009:Proto-Oncogene Proteins c-kit; D019331:NG-Nitroarginine Methyl Ester