Nuyt AM. Antenatal antioxidant prevents adult hypertension, vascular dysfunction, and microvascular rarefaction associated with in utero exposure to a low-protein diet. Am J Physiol Regul Integr Comp Physiol 292: R1236 -R1245, 2007. First published November 30, 2006; doi:10.1152/ajpregu.00227.2006.-Developmental programming of hypertension is associated with vascular dysfunction characterized by impaired vasodilatation to nitric oxide, exaggerated vasoconstriction to ANG II, and microvascular rarefaction appearing in the neonatal period. Hypertensive adults have indices of increased oxidative stress, and newborns that were nutrient depleted during fetal life have decreased antioxidant defenses and increased susceptibility to oxidant injury. To test the hypothesis that oxidative stress participates in early life programming of hypertension, vascular dysfunction, and microvascular rarefaction associated with maternal protein deprivation, pregnant rats were fed a normal, low protein (LP), or LP plus lazaroid (lipid peroxidation inhibitor) isocaloric diet from the day of conception until delivery. Lazaroid administered along with the LP diet prevented blood pressure elevation, enhanced vasomotor response to ANG II, impaired vasodilatation to sodium nitroprusside, and microvascular rarefaction in adult offspring. Liver total glutathione was significantly decreased in LP fetuses, and kidney eight-isoprostaglandin F2␣ (8-isoPGF 2␣) levels were significantly increased in adult LP offspring; these modifications were prevented by lazaroid. Renal nitrotyrosine abundance and blood levels of 1,4-dihydroxynonene and 4-hydroxynonenal-protein adducts were not modified by antenatal diet exposure. This study shows in adult offspring of LP-fed dams prevention of hypertension, vascular dysfunction, microvascular rarefaction, and of an increase in indices of oxidative stress by the administration of lazaroid during gestation. Lazaroid also prevented the decrease in antioxidant glutathione levels in fetuses, suggesting an antenatal mild oxidative stress in offspring of LP-fed dams. These studies support the concept that perinatal oxidative insult can lead to permanent alterations in the cardiovascular system development.hypertension; vascular dysfunction; developmental origin of adult disease; oxidative stress; antioxidants.Cardiovascular diseases represent currently the leading cause of mortality in Western countries. The hypothesis of a developmental origin of these pathologies derives from epidemiological studies, indicating that, independent of genetic or life style factors, the risks of hypertension (HT), stroke, and coronary heart disease in later life are inversely proportional to birth weight. Alteration of the vascular response to ACh, a decreased arterial compliance, and an increased incidence of atherosclerosis are all evidence further illustrating the vascular risk in children and adults born with low birth weight and/or intrauterine growth retardation (3,4,44,47).Experimentally, HT is observed in adults after malnutrit...

In adults, irritable bowel syndrome (IBS) and functional dyspepsia (FD) are chronic conditions that often start during childhood. We investigated mucosal serotonin (5-HT) signalling in children with the idea that data from subjects with a shorter history may improve our understanding of underlying pathophysiological mechanisms. Methods 98 children undergoing gastroscopy or colonoscopy were prospectively studied. Biopsy specimens were evaluated for inflammation, enterochromaffin cell numbers, 5-HT content, and mRNA levels for the synthetic enzyme, tryptophan hydroxylase 1 (TpH1) and the serotonin transporter (SERT) were assessed by quantitative real-time RT-PCR. Results Data from 12 children with IBS and 17 with FD were compared to age-matched controls (12 with rectal biopsies and 12 with gastric biopsies) and to subjects with organic disorders. In patients with FD, a small number of immune cells were observed in the gastric mucosa in half of the patients, but no abnormalities with respect of the 5-HT pathway were identified. In patients with IBS, no differences were detected between patients and controls regarding intraepithelial lymphocytes and CD3+ cells in the lamina propria although all patients exhibited at least a slight inflammatory infiltrate. In the IBS samples, higher 5-HT content (P<0.01) and lower SERT mRNA (P<0.05) were detected as compared to controls. Severe inflammation in the colonic mucosa had a high impact on 5-HT signalling with a significant decrease in EC cells (P<0.01) and 5-HT content (P<0.01) and a high SERT mRNA expression (P<0.01). Conclusion These results confirm in children the role of 5-HT signalling in IBS and argue against such a role in FD.

Regardless of inflammation, NGF content is increased in rectal mucosa of diarrhea-predominant IBS children.

The efficacy of angiotensin-converting enzyme inhibitors (ACEIs) in the treatment of chronic aortic regurgitation (AR) is not well established and remains controversial. The mechanisms by which ACEIs may protect against left-ventricular (LV) volume overload are not well understood, and clinical trials performed until now have yielded conflicting results. This study was therefore performed to assess the effectiveness of two different doses of the ACEI captopril in a rat model of chronic AR. We compared the effects of a 6-month low-dose (LD) (25 mg/kg) or higher dose (HD) (75 mg/kg) treatment with captopril on LV function and hypertrophy in Wistar rats with severe AR. Untreated animals developed LV eccentric hypertrophy and systolic dysfunction. LD treatment did not prevent hypertrophy and provided modest protection against systolic dysfunction. HD treatment preserved LV systolic function and dimensions and tended to slow hypertrophy. The cardiac index remained high and similar among all AR groups, treated or not. Tissue renin-angiotensin system (RAS) analysis revealed that ACE activity was increased in the LVs of AR animals and that only HD treatment significantly decreased angiotensin II receptor mRNA levels. Fibronectin expression was increased in the LV or AR animals, but HD treatment almost completely reversed this increase. The ACE inhibitor captopril was effective at high doses in this model of severe AR. These effects might be related to the modulation of tissue RAS and the control of fibrosis.

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BackgroundSensorimotor impairments secondary to a spinal cord injury affect standing postural balance. While quasi-static postural balance impairments have been documented, little information is known about dynamic postural balance in this population. The aim of this study was to quantify and characterize dynamic postural balance while standing among individuals with a spinal cord injury using the comfortable multidirectional limits of stability test and to explore its association with the quasi-static standing postural balance test.MethodsSixteen individuals with an incomplete spinal cord injury and sixteen able-bodied individuals participated in this study. For the comfortable multidirectional limits of stability test, participants were instructed to lean as far as possible in 8 directions, separated by 45° while standing with each foot on a forceplate and real-time COP visual feedback provided. Measures computed using the center of pressure (COP), such as the absolute maximal distance reached (COPmax) and the total length travelled by the COP to reach the maximal distance (COPlength), were used to characterize performance in each direction. Quasi-static standing postural balance with eyes open was evaluated using time-domain measures of the COP. The difference between the groups and the association between the dynamic and quasi-static test were analyzed.ResultsThe COPlength of individuals with SCI was significantly greater (p ≤ 0.001) than that of able-bodied individuals in all tested directions except in the anterior and posterior directions (p ≤ 0.039), indicating an increased COP trajectory while progressing towards their maximal distance. The COPmax in the anterior direction was significantly smaller for individuals with SCI. Little association was found between the comfortable multidirectional limits of stability test and the quasi-static postural balance test (r ≥ −0.658).ConclusionStanding dynamic postural balance performance in individuals with an incomplete spinal cord injury can be differentiated from that of able-bodied individuals with the comfortable limits of stability test. Performance among individuals with an incomplete spinal cord injury is characterized by lack of precision when reaching. The comfortable limits of stability test provides supplementary information and could serve as an adjunct to the quasi-static test when evaluating postural balance in an incomplete spinal cord injury population.

Multidirectional seated postural stability is reduced in individuals with SCI who have paralysis of the abdominal and lower back muscles in comparison to able-bodied individuals.

Multidirectional-seated postural stability can be predicted almost perfectly by evaluating trunk inclinations performed toward the anterior, left postero-lateral, and right lateral directions.