Ultrastructural localization of nitric oxide synthase and endothelin in rat pulmonary artery and vein during postnatal development and ageing

Abstract.

The ultrastructural distribution of nitric oxide synthase (neuronal isoform, type I) and endothelin immunoreactivity was examined in the developing and ageing male Wistar rat pulmonary artery and vein. This study demonstrates that from birth to old age (24 months) nitric oxide synthase and endothelin are localized within subpopulations of endothelial cells in the pulmonary vasculature. In the pulmonary artery and vein of newborn rats, and pulmonary vein of 24-month-old rats, positive labelling for nitric oxide synthase was also observed in the vascular smooth muscle. During development and ageing there were ultrastructural and immunocytochemical alterations in the intima of the pulmonary artery and vein. In older animals, damaged endothelial cells were seen alongside healthy-appearing cells, rich in cytoplasmic vesicles and endoplasmic reticulum. In contrast to damaged cells, the healthy-appearing endothelial cells displayed positive cytoplasmic labelling for nitric oxide synthase or endothelin. These immunopositive cells also appeared in the altered regions of the vessels where substantial enlargement of subendothelial extracellular matrix and the presence of various forms of degenerating macrophages and large bundles of collagen fibres were evident. Damage to the pulmonary artery was particularly evident at the ages of 12 and 24 months; various forms of macrophages, some of which displayed positive labelling for nitric oxide synthase and endothelin, were present in the altered intimal subendothelial zone. In conclusion, this study on the pulmonary vasculature suggests that endothelin and NOS in endothelial cells play a role in the local control of vascular tone throughout the lifespan of rats, even in older animals when there is intimal thickening and some endothelial damage. NOS and endothelin was also seen in smooth muscle and macrophages at certain stages in postnatal development and ageing.