P C Ursell1, M Mayes. 1. Department of Pathology, University of California at San Francisco 94143-0506, USA.
Abstract
BACKGROUND: Although nitric oxide seems important to cardiovascular function, the ontogenesis of this chemical messenger in the heart is unknown. To investigate this issue, we determined the distribution of nitric oxide synthase (NOS) in the rat heart at different stages during development. METHODS: Immunohistochemistry and the NADPH-diaphorase reaction were used to localize NOS activity-specifically, the endothelial isoform (eNOS) and neuronal isoform (bNOS)-in fetal (14- and 18-day gestation), neonatal (0-, 3-, and 6-day gestation), 12-day-old, 1-month-old, and mature adult Fischer 344 rat hearts. RESULTS: There was sparse eNOS immunoreactivity in the endocardium of the youngest fetal hearts; antibody to eNOS did not localize any vessels within the noncompact myocardium at this stage. By the eighteenth day of embryonic development (e18), eNOS was present not only in endocardium but also in the intima of numerous small vessels within the compact myocardium. In the neonatal rat heart, vascular eNOS predominated, with extensive reaction product in arteries, veins, and numerous capillary size vessels within the myocardium; the endocardium also contained eNOS immunoreactivity. A similar distribution was maintained throughout the remainder of development. Only rare bNOS-immunoreactive neurons were detected in hearts at the three oldest ages. CONCLUSIONS: (1) At e14, eNOS is confined to the endocardium of the developing rat heart; (2) as the myocardium becomes compact, vascular eNOS predominates over endocardial eNOS; (3) at birth, there is extensive eNOS in a distribution similar to the mature pattern; and (4) there is very little bNOS-immunoreactive neural tissue in the rat heart at any stage.
BACKGROUND: Although nitric oxide seems important to cardiovascular function, the ontogenesis of this chemical messenger in the heart is unknown. To investigate this issue, we determined the distribution of nitric oxide synthase (NOS) in the rat heart at different stages during development. METHODS: Immunohistochemistry and the NADPH-diaphorase reaction were used to localize NOS activity-specifically, the endothelial isoform (eNOS) and neuronal isoform (bNOS)-in fetal (14- and 18-day gestation), neonatal (0-, 3-, and 6-day gestation), 12-day-old, 1-month-old, and mature adult Fischer 344 rat hearts. RESULTS: There was sparse eNOS immunoreactivity in the endocardium of the youngest fetal hearts; antibody to eNOS did not localize any vessels within the noncompact myocardium at this stage. By the eighteenth day of embryonic development (e18), eNOS was present not only in endocardium but also in the intima of numerous small vessels within the compact myocardium. In the neonatal rat heart, vascular eNOS predominated, with extensive reaction product in arteries, veins, and numerous capillary size vessels within the myocardium; the endocardium also contained eNOS immunoreactivity. A similar distribution was maintained throughout the remainder of development. Only rare bNOS-immunoreactive neurons were detected in hearts at the three oldest ages. CONCLUSIONS: (1) At e14, eNOS is confined to the endocardium of the developing rat heart; (2) as the myocardium becomes compact, vascular eNOS predominates over endocardial eNOS; (3) at birth, there is extensive eNOS in a distribution similar to the mature pattern; and (4) there is very little bNOS-immunoreactive neural tissue in the rat heart at any stage.
Authors: Liliana Viera; Milka Radmilovich; Marcelo R Vargas; Cassandra N Dennys; Landon Wilson; Stephen Barnes; Maria Clara Franco; Joseph S Beckman; Alvaro G Estévez Journal: Free Radic Biol Med Date: 2012-11-27 Impact factor: 7.376