Maternal fructose intake during pregnancy and lactation: Later effects on renal function.

Excessive fructose consumption has been associated with hypertension and metabolic disorders and can alter physiological adaptations during pregnancy, with long-term detrimental consequences. This study evaluated in post-weaning mothers the effects of increased fructose consumption during pregnancy and lactation on blood pressure and renal function. Female Wistar rats were assigned to one of four experimental groups: non-pregnant control (NPC); pregnant control (PC); non-pregnant fructose (NPF), and pregnant fructose (PF). Control rats had free access to food and water, while the fructose groups had free access to food and to a 20% fructose solution, over the time period of the experiment. The systolic BP and renal function parameters were measured at the end of the experimental period, one week after weaning (28 days after delivery). The results were presented as means ± standard error. Higher values of BP were observed in both pregnant and non-pregnant rats treated with fructose compared to control. Creatinine clearance was reduced only in the PF group; however, both the PF and NPF groups had reduced Na+ and K+ excretions. In the PF group, there was also glomerular enlargement and changes in the media/lumen (M/L) ratio of interlobular arteries. Additionally, the PF group showed increased macrophage infiltration and expression of alpha-SM-actin and reduced expression of nitric-oxide-synthase endothelial in renal tissue. These findings suggest that the association of high fructose intake with pregnancy aggravated kidney changes that persisted for up to four weeks after delivery, which may represent a risk factor for maternal health.

Intermittent hypoxia changes the interaction of the kinin-VEGF system and impairs myocardial angiogenesis in the hypertrophic heart.

Intermittent hypoxia (IH) is a feature of obstructive sleep apnea (OSA), a condition highly associated with hypertension-related cardiovascular diseases. Repeated episodes of IH contribute to imbalance of angiogenic growth factors in the hypertrophic heart, which is key in the progression of cardiovascular complications. In particular, the interaction between vascular endothelial growth factor (VEGF) and the kallikrein-kinin system (KKS) is essential for promoting angiogenesis. However, researchers have yet to investigate experimental models of IH that reproduce OSA, myocardial angiogenesis, and expression of KKS components. We examined temporal changes in cardiac angiogenesis in a mouse IH model. Adult male C57BI/6 J mice were implanted with Matrigel plugs and subjected to IH for 1-5 weeks with subsequent weekly histological evaluation of vascularization. Expression of VEGF and KKS components was also evaluated. After 3 weeks, in vivo myocardial angiogenesis and capillary density were decreased, accompanied by a late increase of VEGF and its type 2 receptor. Furthermore, IH increased left ventricular myocardium expression of the B2 bradykinin receptor, while reducing mRNA levels of B1 receptor. These results suggest that in IH, an unexpected response of the VEGF and KKS systems could explain the reduced capillary density and impaired angiogenesis in the hypoxic heart, with potential implications in hypertrophic heart malfunction.

Afferent innervation of the ischemic kidney contributes to renal dysfunction in renovascular hypertensive rats.

The ablation of renal nerves, by destroying both the sympathetic and afferent fibers, has been shown to be effective in lowering blood pressure in resistant hypertensive patients. However, experimental studies have reported that the removal of sympathetic fibers may lead to side effects, such as the impairment of compensatory cardiorenal responses during a hemodynamic challenge. In the present study, we evaluated the effects of the selective removal of renal afferent fibers on arterial hypertension, renal sympathetic nerve activity, and renal changes in a model of renovascular hypertension. After 4 weeks of clipping the left renal artery, afferent renal denervation (ARD) was performed by exposing the left renal nerve to a 33 mM capsaicin solution for 15 min. After 2 weeks of ARD, we found reduced MAP (~ 18%) and sympathoexcitation to both the ischemic and contralateral kidneys in the hypertensive group. Moreover, a reduction in reactive oxygen species was observed in the ischemic (76%) and contralateral (27%) kidneys in the 2K1C group. In addition, ARD normalized renal function markers and proteinuria and podocin in the contralateral kidney. Taken altogether, we show that the selective removal of afferent fibers is an effective method to reduce MAP and improve renal changes without compromising the function of renal sympathetic fibers in the 2K1C model. Renal afferent nerves may be a new target in neurogenic hypertension and renal dysfunction.

Selective afferent renal denervation mitigates renal and splanchnic sympathetic nerve overactivity and renal function in chronic kidney disease-induced hypertension.

BACKGROUND: Clinical and experimental evidence have shown that renal denervation, by removing both the sympathetic and afferent nerves, improves arterial hypertension and renal function in chronic kidney disease (CKD). Given the key role of renal sympathetic innervation in maintaining sodium and water homeostasis, studies have indicated that the total removal of renal nerves leads to impaired compensatory mechanisms during hemodynamic challenges. METHOD: In the present study, we hypothesized that afferent (or sensory) fibers from the diseased kidney contribute to sympathetic overactivation to the kidney and other target organ, such as the splanchnic region, contributing to hypertension in CKD. We used a method to remove selectively the afferent renal fibers (periaxonal application of 33 mmol/l capsaicin) in a rat model of CKD, the 5/6 nephrectomy. RESULTS: Three weeks after afferent renal denervation (ARD), we found a decrease in mean arterial pressure (∼15%) and normalization in renal and splanchnic sympathetic nerve hyperactivity in the CKD group. Interestingly, intrarenal renin--angiotensin system, as well as renal fibrosis and function and proteinuria were improved after ARD in CKD rats. CONCLUSION: The findings demonstrate that afferent fibers contribute to the maintenance of arterial hypertension and reduced renal function that are likely to be mediated by increased sympathetic nerve activity to the renal territory as well as to other target organs in CKD.

Renal denervation reduces sympathetic overactivation, brain oxidative stress, and renal injury in rats with renovascular hypertension independent of its effects on reducing blood pressure.

The underlying mechanisms by which renal denervation (RD) decreases blood pressure (BP) remain incompletely understood. In this study, we investigated the effects of ischemic kidney denervation on different sympathetic outflows, brain and renal expression of angiotensin-II receptors, oxidative stress and renal function markers in the 2-kidney, 1-clip (2K-1C) rat model. Surgical RD was performed in Wistar male rats 4-5 weeks after clip implantation. After 10 days of RD, BP, and the activity of sympathetic nerves projecting to the contralateral kidney (rSNA) and splanchnic region were partially reduced in 2K-1C rats, with no change in systemic renin-angiotensin system (RAS). To distinguish the effects of RD from the reduction in BP, 2K-1C rats were treated with hydralazine by oral gavage (25 mg/kg/day for 1 week). RD, but not hydralazine, normalized oxidative stress in the sympathetic premotor brain regions and improved intrarenal RAS, renal injury, and proteinuria. Furthermore, different mechanisms led to renal injury and oxidative stress in the ischemic and contralateral kidneys of 2K-1C rats. Injury and oxidative stress in the ischemic kidney were driven by the renal nerves. Although RD attenuated rSNA, injury and oxidative stress persisted in the contralateral kidney, probably due to increased BP. Therefore, nerves from the ischemic kidney at least partially contribute to the increase in BP, sympathetic outflows, brain oxidative stress, and renal alterations in rats with renovascular hypertension. Based on these findings, the reduction in oxidative stress in the brain is a central mechanism that contributes to the effects of RD on Goldblatt hypertension.

Total renal denervation reduces sympathoexcitation to different target organs in a model of chronic kidney disease.

It is known that increased sympathetic nerve activity in chronic kidney disease (CKD) progressively worsens kidney function and hypertension. We tested the hypothesis that total renal denervation contributes to reduce sympathetic activation to different beds and improves renal function in 5/6 nephrectomy model of CKD in male Wistar rats. After eight weeks of 5/6 nephrectomy surgery there was an increase in mean arterial pressure (CKD 179±22mmHg, n=6 vs. control animals 108±9; p<0.05, n=6) with no changes in heart rate (HR). Sympathetic nerve activity was increased at different levels to the remaining kidney, splanchnic and lumbar beds compared to control (CTL) group (CKD rSNA: 150±50, n=9 vs. CTL 96±15, n=9; CKD sSNA: 129±51, n=5 vs. CTL 34±14, n=6; CKD lSNA: 203±35, n=8 vs. CTL 146±21, spikes/s, n=7, p<0.05). Three weeks after total renal denervation (DNX) MAP was normalized in the CKD rats (124±19mmHg, n=5, p<0.05), with no change in HR. The lSNA was normalized (151±40, n=5, vs. CKD 203±35 spikes/s, n=8) and sSNA was decreased in 49% (64±34, n=5 vs. CKD 129±51 spikes/s, n=5, p<0.05). Renal function, assessed by creatinine plasma levels was improved after renal denervation (CKD 1.50±0.64, n=8; vs. CKD+DNX 0.82±0.22mg/mL, n=8, p<0.05). These findings demonstrate that renal nerves contribute to the maintenance of hypertension in CKD by increasing sympathoexcitation to other beds.

Sleep restriction during pregnancy and its effects on blood pressure and renal function among female offspring.

The influence of sleep restriction (SR) during pregnancy on blood pressure and renal function among female adult offspring was investigated. Pregnant Wistar rats were distributed into control and SR groups. The SR was performed between the 14th and 20th days of pregnancy (multiple platforms method for 20 h/day). At 2 months of age, half of the offspring from both groups were subjected to an ovariectomy (ovx), and the other half underwent sham surgery. The groups were as follows: control sham (Csham), control ovx (Covx), SR sham (SRsham), and SR ovx (SRovx). Renal function markers and systolic blood pressure (BPi, indirect method) were evaluated at 4, 6, and 8 months. Subsequently, the rats were euthanized, kidneys were removed, and processed for morphological analyses of glomerular area (GA), number of glomeruli per mm3 (NG), and kidney mass (KM). Increased BPi was observed in the Covx, SRsham, and SRovx groups compared to Csham at all ages. Increased plasma creatinine concentration and decreased creatinine clearance were observed in the SRsham and SRovx groups compared to the Csham and Covx groups. The SRovx group showed higher BPi and reduced creatinine clearance compared to all other groups. The SRovx group showed reduced values of GA and KM, as well as increased NG, macrophage infiltration, collagen deposit, and ACE1 expression at the renal cortex. Therefore, SR during pregnancy might be an additional risk factor for developing renal dysfunction and increasing BP in female adult offspring. The absence of female hormones exacerbates the changes caused by SR.

Autonomic and Renal Alterations in the Offspring of Sleep-Restricted Mothers During Late Pregnancy.

OBJECTIVES: Considering that changes in the maternal environment may result in changes in progeny, the aim of this study was to investigate the influence of sleep restriction during the last week of pregnancy on renal function and autonomic responses in male descendants at an adult age. METHODS: After confirmation of pregnancy, female Wistar rats were randomly assigned to either a control or a sleep restriction group. The sleep-restricted rats were subjected to sleep restriction using the multiple platforms method for over 20 hours per day between the 14th and 20th day of pregnancy. After delivery, the litters were limited to 6 offspring that were designated as offspring from control and offspring from sleep-restricted mothers. Indirect measurements of systolic blood pressure (BPi), renal plasma flow, glomerular filtration rate, glomerular area and number of glomeruli per field were evaluated at three months of age. Direct measurements of cardiovascular function (heart rate and mean arterial pressure), cardiac sympathetic tone, cardiac parasympathetic tone, and baroreflex sensitivity were evaluated at four months of age. RESULTS: The sleep-restricted offspring presented increases in BPi, glomerular filtration rate and glomerular area compared with the control offspring. The sleep-restricted offspring also showed higher basal heart rate, increased mean arterial pressure, increased sympathetic cardiac tone, decreased parasympathetic cardiac tone and reduced baroreflex sensitivity. CONCLUSIONS: Our data suggest that reductions in sleep during the last week of pregnancy lead to alterations in cardiovascular autonomic regulation and renal morpho-functional changes in offspring, triggering increases in blood pressure.

Autonomic and Renal Alterations in the Offspring of Sleep-Restricted Mothers During Late Pregnancy

OBJECTIVES: Considering that changes in the maternal environment may result in changes in progeny, the aim of this study was to investigate the influence of sleep restriction during the last week of pregnancy on renal function and autonomic responses in male descendants at an adult age. METHODS: After confirmation of pregnancy, female Wistar rats were randomly assigned to either a control or a sleep restriction group. The sleep-restricted rats were subjected to sleep restriction using the multiple platforms method for over 20 hours per day between the 14th and 20th day of pregnancy. After delivery, the litters were limited to 6 offspring that were designated as offspring from control and offspring from sleep-restricted mothers. Indirect measurements of systolic blood pressure (BPi), renal plasma flow, glomerular filtration rate, glomerular area and number of glomeruli per field were evaluated at three months of age. Direct measurements of cardiovascular function (heart rate and mean arterial pressure), cardiac sympathetic tone, cardiac parasympathetic tone, and baroreflex sensitivity were evaluated at four months of age. RESULTS: The sleep-restricted offspring presented increases in BPi, glomerular filtration rate and glomerular area compared with the control offspring. The sleep-restricted offspring also showed higher basal heart rate, increased mean arterial pressure, increased sympathetic cardiac tone, decreased parasympathetic cardiac tone and reduced baroreflex sensitivity. CONCLUSIONS: Our data suggest that reductions in sleep during the last week of pregnancy lead to alterations in cardiovascular autonomic regulation and renal morpho-functional changes in offspring, triggering increases in blood pressure.

Aldosterone Contributes to Sympathoexcitation in Renovascular Hypertension.

BACKGROUND: Although angiotensin II (Ang II) is essential to the development of renovascular hypertension, aldosterone plays a role as well. Recent studies have demonstrated a cross-talk between Ang II type 1 and mineralocorticoid receptors in the brain and kidneys. However, the role of aldosterone in the autonomic and renal dysfunction of renovascular hypertension is not well understood. AIM: The current study evaluated whether aldosterone contributes to cardiovascular and renal dysfunction in the 2 kidney-1 clip (2K1C) model. METHODS: Mean arterial pressure (MAP) and baroreceptor reflex for control of the heart rate were evaluated in 2K1C treated or not treated with spironolactone (200mg/kg/day, 7 days). Tonic and reflex control of renal sympathetic nerve activity (rSNA) were assessed in urethane-anaesthetized rats. Plasma renin activity (PRA), kidney renin protein expression, renal injury, and central AT1 receptor protein expression were assessed. RESULTS: Spiro reduced MAP (198±4 vs. 170±9mm Hg; P < 0.05), normalized rSNA (147±9 vs. 96±10 pps; P < 0.05), and increased renal baroreceptor reflex sensitivity in the 2K1C rats. Spiro reduced α-smooth muscle actin expression in the nonclipped kidney in the 2K1C group (5±0.6 vs. 1.1±0.2%; P < 0.05). There was no change in PRA; however, a decrease in renin protein expression in the nonclipped kidney was found in the 2K1C treated group (217±30 vs. 160±19%; P < 0.05). Spiro treatment decreased AT1 receptor in the central nervous system (CNS) only in 2K1C rats (138±10 vs. 84±12%; P < 0.05). CONCLUSION: Aldosterone contributes to autonomic dysfunction and intrarenal injury in 2K1C, these effects are mediated by the CNS.

Chronic sleep restriction during pregnancy--repercussion on cardiovascular and renal functioning of male offspring.

Changes in the maternal environment can induce fetal adaptations that result in the progression of chronic diseases in the offspring. The objective of the present study was to evaluate the effects of maternal chronic sleep restriction on blood pressure, renal function and cardiac baroreflex response on male offspring at adult age. Female 3-month-old Wistar rats were divided in two experimental groups: control (C) and chronic sleep restricted (CSR). Pregnancy was confirmed by vaginal smear. Chronic sleep restricted females were subjected to sleep restriction by the multiple platform technique for 20 h daily, between the 1st and 20th day of pregnancy. After birth, the litters were reduced to 6 rats per mother, and were designated as offspring from control (OC) and offspring from chronic sleep restricted (OCSR). Indirect blood pressure (BPi - tail cuff) was measured by plethysmography in male offspring at 3 months old. Following, the renal function and cardiac baroreflex response were analyzed. Values of BPi in OCSR were significantly higher compared to OC [OC: 127 ± 2.6 (19); OCSR: 144 ± 2.5 (17) mmHg]. The baroreflex sensitivity to the increase of blood pressure was reduced in OCSR [Slope: OC: -2.6 ± 0.15 (9); OCRS: -1.6 ± 0.13 (9)]. Hypothalamic activity of ACE2 was significantly reduced in OCSR compared to OC [OC: 97.4 ± 15 (18); OSR: 60.2 ± 3.6 (16) UAF/min/protein mg]. Renal function alteration was noticed by the increase in glomerular filtration rate (GFR) observed in OCSR [OC: 6.4 ± 0.2 (10); OCSR: 7.4 ± 0.3 (7)]. Chronic sleep restriction during pregnancy caused in the offspring hypertension, altered cardiac baroreflex response, reduced ACE-2 activity in the hypothalamus and renal alterations. Our data suggest that the reduction of sleeping time along the pregnancy is able to modify maternal homeostasis leading to functional alterations in offspring.

[Histomorphometric differences between the left and right internal thoracic arteries in humans]. / Diferenças histomorfométricas entre as artérias torácicas internas esquerda e direita em humanos.

OBJECTIVE: The use of the left internal thoracic artery in coronary artery bypass surgery is currently recognized as the best option, providing lesser incidence of cardiovascular events and superior long-term survival. As a result, great expansion of bilateral internal thoracic artery (ITAs) grafts has been observed, with additional demonstration of improved long-term survival. Therefore the aim of this study was to examine and compare the histomorphometric structure among different segments of the left and right ITA. METHOD: Specimens of ITAs harvested from 18 cadavers were divided in nine proportional segments. Cuts of each segment had been stained with hematoxylin-eosin and Verhoeff-Van Gieson technique. The following parameters had been analyzed: perimeter of the arterial lumen, thickness of the intima, thickness of the media layer and amount of elastic fiber in the media layer. RESULTS: The perimeter of both ATIs decreases downstream its course, the proximal segments of the right ITA exhibit perimeter significantly greater than left ITA The analysis of the intima thickness revealed no significant difference between left and right ITA, except in the segment 9. The thickness of media layer showed no statistical difference between them, except in the segment 1. The number of elastic layers in the distal left ITA segments is significantly higher than right ITA. CONCLUSION: Data analyses from this study suggest structural differences between the left and right internal thoracic arteries.

Diferenças histomorfométricas entre as artérias torácicas internas esquerda e direita em humanos / Histomorphometric differences between the left and right internal thoracic arteries in humans

OBJETIVO: O uso do enxerto de artéria torácica interna esquerda (ATIE) é atualmente reconhecido como a melhor opção na cirurgia de revascularização miocárdica, proporcionando menor incidência tardia de eventos cardiovasculares e maior sobrevida. Conseqüentemente, houve grande incremento nas últimas décadas do uso bilateral das artérias torácicas internas (ATIs), com demonstração de melhora adicional de sobrevida em longo-termo. O objetivo desse trabalho foi estudar a estrutura histológica das ATIs esquerda e direita (ATID), com a análise histomorfométrica seqüencial e comparativa entre os segmentos das duas artérias. MÉTODOS: Foram estudados espécimes de ATIs retirados de 18 cadáveres, divididos em nove segmentos proporcionais. Cortes de cada segmento foram corados com técnica de hematoxilina-eosina e Verhoeff-Van Gieson. Foram analisados os seguintes parâmetros: perímetro da luz arterial, espessura da íntima, espessura da camada média e quantidade de fibras elásticas da camada média. RESULTADOS: O perímetro interno de ambas as ATIs diminuiu ao longo do percurso, dos segmentos mais proximais para os mais distais. Os segmentos proximais da ATID apresentaram perímetro significativamente maiores do que os da ATIE. A análise da espessura da íntima revelou não existir diferença significativa entre ATIE e ATID, exceto no segmento 1. A espessura da camada média diminuiu ao longo da extensão das ATIs, não havendo diferença estatística entre elas, exceto no segmento 9. O número de lâminas elásticas nos segmentos distais da ATIE foi estatisticamente superior ao da ATID. CONCLUSÃO: Portanto, os dados do presente estudo sugerem haver diferenças estruturais entre as ATIs direita e esquerda.

OBJECTIVE: The use of the left internal thoracic artery in coronary artery bypass surgery is currently recognized as the best option, providing lesser incidence of cardiovascular events and superior long-term survival. As a result, great expansion of bilateral internal thoracic artery (ITAs) grafts has been observed, with additional demonstration of improved long-term survival. Therefore the aim of this study was to examine and compare the histomorphometric structure among different segments of the left and right ITA. METHOD: Specimens of ITAs harvested from 18 cadavers were divided in nine proportional segments. Cuts of each segment had been stained with hematoxylin-eosin and Verhoeff-Van Gieson technique. The following parameters had been analyzed: perimeter of the arterial lumen, thickness of the intima, thickness of the media layer and amount of elastic fiber in the media layer. RESULTS: The perimeter of both ATIs decreases downstream its course, the proximal segments of the right ITA exhibit perimeter significantly greater than left ITA The analysis of the intima thickness revealed no significant difference between left and right ITA, except in the segment 9. The thickness of media layer showed no statistical difference between them, except in the segment 1. The number of elastic layers in the distal left ITA segments is significantly higher than right ITA. CONCLUSION: Data analyses from this study suggest structural differences between the left and right internal thoracic arteries.

Estudo histomorfométrico seqüencial da artéria torácica interna esquerda / Sequential histomorphometric study of the left internal thoracic artery

OBJETIVO: O uso de enxertos de artéria torácica interna esquerda (ATIE) é atualmente reconhecido como a melhor opção na cirurgia de revascularização miocárdica, proporcionando menor incidência de eventos cardiovasculares e maior sobrevida. Entretanto, com a expansão do uso dos enxertos arteriais, faz se necessário melhor entendimento da estrutura histológica da ATIE. Portanto, o objetivo deste trabalho foi estudar a estrutura histológica da ATIE e a análise histomorfométrica seqüencial e comparativa entre os diferentes segmentos. MÉTODO: Foram estudados espécimes de ATIE retirados de 18 cadáveres, divididos em nove segmentos proporcionais. Cortes de cada segmento foram corados com técnica de Verhoeff-Van Gieson. Foram analisados os seguintes parâmetros: perímetro da luz arterial, espessura da íntima, espessura da camada média, número de fibras elásticas da camada média e a densidade de fibras elásticas. RESULTADOS: Os dados obtidos mostraram que perímetro da ATIE mostra tendência a diminuir ao longo de sua extensão, a espessura da íntima é aumentada nos segmentos proximais, a espessura da camada média diminui ao longo de sua extensão, o número de lâminas elásticas se concentra nos segmentos intermediários, a densidade de lâminas elásticas é diminuída nos segmentos proximais e distais. CONCLUSÃO: Portanto, os achados do presente estudo confirmam a heterogeneidade da estrutura histológica seqüencial da ATIE.

OBJECTIVE: The use of left internal thoracic artery (LITA) in coronary artery bypass surgery is currently recognized as the best option, providing lower incidences of cardiovascular events and superior long-term survival. Now, incremental utilization of these grafts makes a reassessment of its histological structure necessary. Therefore, the purpose of this study was to examine and compare the sequential histological structure of LITA. METHOD: Specimens of LITA harvested from 18 cadavers, divided into nine proportional segments, were studied. Cuts of each segment were stained by the Verhoeff-Van Gieson technique. The following parameters were analyzed: perimeter of the arterial lumen, thickness of the intima, thickness of the media layer, amount of elastic fiber in the media layer and the elastic fiber density. RESULTS: The collected data showed that perimeter of the LITA decreases downstream on its course, the thickness of the intima is increased in the proximal segments, the thickness of the media layer diminishes throughout its extension, the number of elastic fibers is concentrated in the intermediate segments and the density of elastic fibers is reduced in the proximal and distal segments. CONCLUSION: Therefore, the findings of the present study validate the heterogeneity of the LITA sequential histological structure.

Long-term effects of maternal diabetes on vascular reactivity and renal function in rat male offspring.

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 endothelium-dependent 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.