Inducible nitric oxide synthase in the myocard

Recognition of significance of nitric oxide synthases (NOS) in cardiovascul ar regulations has led to intensive research and development of therapies f ocused on NOS as potential therapeutic targets. However, the NOS isoform pr ofile of cardiac tissue and subcellular localization of NOS isoforms remain a matter of debate. The aim of this study was to investigate the localizat ion of an inducible NOS isoform (NOS2) in cardiomyocytes. Employing a novel immunocytochemical technique of a catalyzed reporter deposition system wit h tyramide and electron microscopical immunocytochemistry complemented with Western blotting and RT-PCR, we detected NOS2 both in rat neonatal and adu lt cultured cardiomyocytes and in the normal myocard of adult rats as well as in the human myocard of patients with dilative cardiomyopathy. NOS2 was targeted predominantly to a particulate component of the cardiomyocyte - al ong contractile fibers, in the plasma membrane including T-tubules, as well as in the nuclear envelope, mitochondria and Golgi complex. Our results po int to an involvement of NOS2 in maintaining cardiac homeostasis and contra dict to the notion that NOS2 is expressed in cardiac tissue only in respons e to various physiological and pathogenic factors. NOS2 targeting to mitoch ondria and contractile fibers suggests a relationship of NO with contractil e function and energy production in the cardiac muscle.