Pulmonary soluble guanylate cyclase, a nitric oxide receptor, is increased during the perinatal period. Bloch, Kenneth D., Galina Filippov, Lucienne S. Sanchez, Masaki Nakane, and Suzanne M. De La Monte. Cardiovascular Research Center and the Cancer Center of the Medical Services and the Departments of & Anesthesia and Pathology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, and Abbott Laboratories, Inc., Abbott Park, IL.
APStracts 3:0227L, 1996.
Nitric oxide (NO) has an important role in the pulmonary vasodilatation associated with the transition from fetal to neonatal life. NO activates pulmonary soluble guanylate cyclase (sGC), an obligate heterodimer composed of [alpha]1 and [beta]1 subunits, increasing synthesis of cGMP and leading to vasodilation. In this study, regulation of sGC subunit expression during pulmonary development was examined. RNA blot hybridization revealed abundant [alpha]1 and [beta]1 subunit mRNA in lungs of late-gestation fetal and neonatal Sprague-Dawley rats, with markedly reduced levels detected in adult lungs. Pulmonary sGC enzyme activity in the presence of 1 mM sodium nitroprusside, a NO-donor compound, was approximately 7-fold greater in 1- and 8-day old rats than in- adult rats (p<0.03). Using immunoblot techniques, pulmonary [alpha]1 subunit concentrations closely correlated with mRNA levels. Using in situ hybridization, [alpha]1 and [beta]1 subunit mRNAs were readily detected in pulmonary vascular and bronchial smooth muscle cells, as well as alveolar and serosal epithelial cells in lungs of 1-day old rats. In adult lungs, sGC subunit mRNAs were present at low levels and were found nearly exclusively in bronchial and vascular smooth muscle cells. These results demonstrate that abundant pulmonary sGC is available to respond to the increased NO produced during the perinatal period. High level expression of sGC subunit genes outside the vasculature of lungs of 1-day old rats suggests an important role for NO/cGMP signal transduction in the perinatal regulation of pulmonary epithelial function and bronchial tone. 

Received 18 April 1996; accepted in final form 14 October 1996.
APS Manuscript Number L121-6.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996