Fetal kidney programming by maternal smoking exposure: effects on kidney structure, blood pressure and urinary sodium excretion in adult offspring.

INTRODUCTION: Fetal programming by different insults results in low birth weight and reduction in nephron number increasing the risk for adult development of cardiovascular and renal diseases. Maternal smoking is an important modifiable adverse fetal exposure worldwide and leads to a decrease in the offspring's birth weight. Thus far, the specific adverse fetal smoking exposures and mechanisms underlying these associations on renal development and functional disorder are unclear. METHODS: The present study investigates, in adult male rats, the effect of smoking exposure (Sk) in uteri on blood pressure (BP) by an indirect tail-cuff method using an electrosphygmomanometer, and its association with nephron structure by stereological estimation, immunohistochemical and histological techniques, in parallel with kidney function creatinine and lithium clearance. RESULTS: The current study showed in a 16-week old Sk offspring enhanced arterial blood pressure associated with, reduced urinary sodium excretion and higher TGF-ß1 glomerular expression. Sk glomeruli also presented an upregulated collagen and fibronectin deposition intrinsically related to fibrotic process as compared to age-matched control group. CONCLUSION: Here, we demonstrate that fetal-programmed Sk offspring present pronounced glomerular TGF-ß1 and fibrotic marker expression that may, subsequently, promote a glomerular epithelial-mesenchymal transition activated process in an Sk offspring. Although the precise mechanism responsible for the subsequently renal morphological and functional response in Sk offspring is incompletely known, the current data suggest that changes in renal function are conducive to excess sodium tubule reabsorption that is associated with enhanced TGF-ß1, fibronectin and collagen deposition, intrinsically related to fibrotic process, might potentiate the programming of adult hypertension.

Dermatan sulfate and bone marrow mononuclear cells used as a new therapeutic strategy after arterial injury in mice.

BACKGROUND AIMS: Previously, we have demonstrated that administration of dermatan sulfate (DS) suppresses neointima formation in the mouse carotid artery by activating heparin co-factor II. A similar suppressive effect was observed by increasing the number of progenitor cells in circulation. In this study, we investigated the combination of DS and bone marrow mononuclear cells (MNC), which includes potential endothelial progenitors, in neointima formation after arterial injury. METHODS: Arterial injury was induced by mechanical dilation of the left common carotid artery. We analyzed the extension of endothelial lesion, thrombus formation, P-selectin expression and CD45(+) cell accumulation 1 and 3 days post-injury, and neointima formation 21 days post-injury. Animals were injected with MNC with or without DS during the first 48 h after injury. RESULTS: The extension of endothelial lesion was similar in all groups 1 day after surgery; however, in injured animals treated with MNC and DS the endothelium recovery seemed to be more efficient 21 days after lesion. Treatment with DS inhibited thrombosis, decreased CD45(+) cell accumulation and P-selectin expression at the site of injury, and reduced the neointimal area by 56%. Treatment with MNC reduced the neointimal area by 54%. The combination of DS and MNC reduced neointima formation by more than 91%. In addition, DS promoted a greater accumulation of MNC at the site of injury. CONCLUSIONS: DS inhibits the initial thrombotic and inflammatory processes after arterial injury and promotes migration of MNC to the site of the lesion, where they may assist in the recovery of the injured endothelium.