ENDOTHELIAL ISOFORM OF NITRIC-OXIDE SYNTHASE IN RAT-HEART INCREASES DURING DEVELOPMENT

Background: Although nitric oxide seems important to cardiovascular fu nction, the ontogenesis of this chemical messenger in the heart is unk nown. To investigate this issue, we determined the distribution of nit ric oxide synthase (NOS) in the rat heart at different stages during d evelopment. Methods: Immunohistochemistry and the NADPH-diaphorase rea ction were used to localize NOS activity-specifically, the endothelial isoform (eNOS) and neuronal isoform (bNOS)-in fetal (14- and 18-day g estation), neonatal (0-, 3-, and 6-day gestation), 12-day-old, 1-month -old, and mature adult Fischer 344 rat hearts. Results: There was spar se eNOS immunoreactivity in the endocardium of the youngest fetal hear ts; antibody to eNOS did not localize any vessels within the noncompac t myocardium at this stage. By the eighteenth day of embryonic develop ment (e18), eNOS was present not only in endocardium but also in the i ntima of numerous small vessels within the compact myocardium. In the neonatal rat heart, vascular eNOS predominated, with extensive reactio n product in arteries, veins, and numerous capillary size vessels with in the myocardium; the endocardium also contained eNOS immunoreactivit y. A similar distribution was maintained throughout the remainder of d evelopment. Only rare bNOS-imnunoreactive neurons were detected in hea rts at the three oldest ages. Conclusions: (1) At e14, eNOS is confine d to the endocardium of the developing rat heart; (2) as the myocardiu m 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 neura l tissue in the rat heart at any stage. (C) 1996 Wiley-Liss, Inc.