Fetal growth impairment can occur in pregnancy complicated by diabetes. Although several studies have focused the effects of nutritional status on intrauterine development, the long-term impact of maternal diabetes on vascular and renal function in the offspring is poorly investigated. In the present study, blood pressure profiles and renal function parameters were investigated in the offspring of diabetic rats (DO). Female rats were made diabetic throughout gestation with a single dose of streptozotocyn (STZ) 10 d before mating. After weaning, the offspring had free access to food and water. Arterial pressure was evaluated every 15 d. Functional and morphometric kidney studies were performed in newborn, 3, 6 and 12-mo-old male rats in DO and in controls, C. Although maternal diabetes did not affect nephron number in the young adult rat, glomerular hypertrophy developed from 3 mo on. Glomerular Filtration Rate and Renal Plasma Flow were observed to be significantly decreased in DO when compared with C, from 3 mo on. In DO, hypertension was observed from 8 wk on and persisted elevated throughout the experimental period (12 mo). Vascular reactivity, evaluated in mesenteric arterial bed showed a decreased endotheliumdependent vasodilatation in 12-mo-old DO animals, while preserved response to sodium nitroprusside was demonstrated. Our data show that exposure to intrauterine diabetes induced by STZ does not affect nephron number in the young offspring but can cause permanent changes in Nitric Oxide (NO)-related vascular response, which, in turn may accelerate the natural age-related nephron loss. Maternal status can affect several physiologic functions of the newborn. In addition, correlation between fetal growth conditions and susceptibility to a number of adult chronic diseases, including coronary heart disease, stroke and hypertension have been identified (1-4). Recently, we have demonstrated that maternal undernutrition promoted development of adult hypertension, impairment of the renal and endothelium functions, decreased absolute number of the nephrons and hypertrophy of the remaining glomeruli in the adult offspring (5-7). Although several experimental studies have focused the effects of the maternal undernutrition on fetal "programming" of adulthood disease, less attention has been paid to the possible in utero late effects of maternal diabetes. In fact, diabetes mellitus can impose several threats both to the mother and the offspring. Experimental and clinical studies have demonstrated that diabetic pregnancy increases the risk of intrauterine death, prematurity, perinatal mortality and congenital malformations (8 -12). Indeed, Chugh et al. (13) have demonstrated that a sustained exposure of the fetus to elevated concentration of glucose may result in diabetic embryopathy, which is characterized by a multitude of congenital birth defects, including those of the nervous, cardiovascular, skeletal, and renal systems. These malformations result from defects occurring in early organogenesis including failure of ...

The present study was designed to evaluate the effects of L-arginine (L-arg) supplementation on blood pressure, vascular nitric oxide content, and renal morphometry in the adult offspring from diabetic mothers. Diabetes mellitus was induced in female rats with a single dose of streptozotocin (50 mg/kg), before mating. The offspring was divided into four groups: group C (controls); group DO (diabetic offspring); group CA (controls receiving 2% L-arg solution dissolved in 2% sucrose in the drinking water) and group DA (DO receiving the L-arg solution). Oral supplementation began after weaning and continued until the end of the experiments. In DO, hypertension was observed, from 3 mo on. In DA, pressure levels were not different from C and CA. In 6-mo-old animals, basal NO production (assessed by DAF-2) was significantly depressed in DO in comparison to controls. The NO production was significantly increased after stimulation with Ach or BK in all groups, the increase being greater in control than in DO rats. L-Arg was able to improve the NO production and to prevent the glomerular hypertrophy in the DO. Our data suggest that the bioavailability of NO is reduced in the DO, because L-arg corrected both the hypertension and glomerular hypertrophy. T he correlation between fetal growth conditions and susceptibility to several pathologies in adulthood, including hypertension, diabetes, stroke, and coronary heart disease, have been identified (1-3). Maternal diabetes has been long known to be a clinical condition that is associated with high rates of spontaneous abortion, congenital malformations and perinatal mortality (4 -7). The malformations result from defects occurring in early organogenesis including failure of neural tube closure, caudal regression syndrome, and urogenital abnormalities, which can be as severe as renal agenesis (8,9). On the other hand, several studies suggested that offspring of diabetic mothers might be at an increased risk for the development of vascular disease and diabetes later in life (10 -12). Holemans et al. (13) have suggested that maternal diabetes may also have lasting adverse consequences on cardiovascular function of the next generation, particularly because offspring of diabetic pregnant rats demonstrate overt insulin resistance in adulthood. Impaired nephrogenesis has been shown in the offspring from rats submitted to hyperglycemia during pregnancy (14).In a previous study, we have demonstrated that maternal diabetes promotes remarkable changes in both kidney function and vascular reactivity in the mature offspring (15). Our data concerning diabetic offspring model (DO) pointed to an interesting model in which, although a normal nephron number was observed, two important factors-systemic hypertension and glomerular hypertrophy-which contribute to the progression of renal disease, were present. In fact, a significant increase in glomerular area concomitant to decreases in renal functional parameters was observed in 3-, 6-, and 12 mo-old DO. In 12-mo-old rats, a decrease...