The Expression Pattern of Nitric Oxide-sensitive Guanylyl Cyclase in the Rat Heart Changes During Postnatal DevelopmentSönke Behrendsa, Andrea Mietensb, Jörg Kempferta, Markus Koglina, Hasso Scholza, and Ralf Middendorffba Institutes of Pharmacology, University Clinic HamburgEppendorf, Hamburg, Germany b Anatomy, University Clinic HamburgEppendorf, Hamburg, Germany Correspondence to: Sönke Behrends, University Clinic HamburgEppendorf, Pharmacology, Martinistrasse 52, 20246 Hamburg, Germany. E-mail: behrends@uke.uni-hamburg.de Nitric oxide (NO)-releasing drugs such as glyceryl trinitrate have been used in the treatment of ischemic heart disease for more than a century. Nevertheless, a detailed analysis of the expression of the NO target enzyme soluble guanylyl cyclase (sGC) in the heart is missing. The aim of the current study was to elucidate the expression, cell distribution, and activity of sGC in the rat heart during postnatal development. Using a novel antibody raised against a C-terminal peptide of the rat ß1-subunit of sGC, the enzyme was demonstrated in early postnatal and adult hearts by Western blotting analyses, showing maximal expression in 10-day-old animals. Measurements of basal, NO-, and NO/YC-1-stimulated sGC activity revealed an increase of sGC activity in hearts from neonatal to 10-day-old rats, followed by a subsequent decrease in adult animals. As shown by immunohistochemical analysis, sGC expression was present in vascular endothelium and smooth muscle cells in neonatal heart but expression shifted to endothelial cells in adult animals. In isolated cardiomyocytes, sGC activity was not detectable under basal conditions but significant sGC activity could be detected in the presence of NO. An increase in expression during the perinatal period and changes in the cell types expressing sGC at different phases of development suggest dynamic regulation rather than constitutive expression of the NO receptor in the heart. (J Histochem Cytochem 50:13251331, 2002) Key Words: nitric oxide, soluble guanylyl cyclase, cardiomyocyte, endothelium, smooth muscle cell
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