Role of heme oxygenase in the regulation of the renal hemodynamics in a model of sex-dependent programmed hypertension by maternal diabetes.

Intrauterine programming of cardiovascular and renal function occurs in diabetes because of the adverse maternal environment. Heme oxygenase 1 (HO-1) and -2 (HO-2) exert vasodilatory and antioxidant actions, particularly in conditions of elevated HO-1 expression or deficient nitric oxide levels. We evaluated whether the activity of the heme-HO system is differentially regulated by oxidative stress in the female offspring of diabetic mothers, contributing to the improved cardiovascular function in comparison with males. Diabetes was induced in pregnant rats by a single dose of streptozotocin (STZ, 50 mg/kg ip) in late gestation. Three-month-old male offspring from diabetic mothers (MODs) exhibited higher blood pressure (BP), higher renal vascular resistance (RVR), worse endothelium-dependent response to acetylcholine (ACH), and an increased constrictor response to phenylephrine (PHE) compared with those in age-matched female offspring of diabetic mothers (FODs), which were abolished by chronic tempol (1 mM) treatment. In anesthetized animals, stannous mesoporphyrin (SnMP; 40 µmol/kg iv) administration, to inhibit HO activity, increased RVR in FODs and reduced glomerular filtration rate (GFR) in MODs, without altering these parameters in control animals. When compared with MODs, FODs showed lower nitrotirosyne levels and higher HO-1 protein expression in renal homogenates. Indeed, chronic treatment with tempol in MODs prevented elevations in nitrotyrosine levels and the acute renal hemodynamics response to SnMP. Then, maternal diabetes results in sex-specific hypertension and renal alterations associated with oxidative stress mainly in adult male offspring, which are reduced in the female offspring by elevation in HO-1 expression and lower oxidative stress levels.

Adiponectin agonist treatment in diabetic pregnant rats.

Gestational diabetes mellitus (GDM) reduces maternal adiponectin and docosahexaenoic acid (DHA) materno-fetal transfer, which may have negative consequences for the offspring. Our aim was to evaluate the effects of the administration of a novel adiponectin agonist (AdipoRon) to GDM rats on the long-term consequences in glycaemia and fatty acids (FA) profile in the offspring. Pregnant rats were randomized to three groups: GDM rats (GDM, n = 8), GDM rats treated with AdipoRon (GDM + ADI, n = 9), and control rats (n = 10). Diabetes was induced with streptozotocin (50 mg/kg) on day 12 of gestation. GDM+ADI received 50 mg/kg/day AdipoRon from day 14 until delivery. Glycaemia and FA profile were determined in mothers and adult offspring (12 weeks old). AdipoRon tended to reduce fasting glucose in diabetic mothers. Diabetic rats presented the foetus with intrauterine growth restriction and higher adiposity, which tried to be counteracted by AdipoRon. In the adult offspring, both GDM + ADI and control animals showed better glucose recovery after oral glucose overload with respect to GDM. DHA in offspring plasma was significantly reduced in both GDM and GDM + ADI compared to controls (P = 0.043). Nevertheless, n-6/n-3 polyunsaturated FA (PUFA) ratio improved in plasma of GDM + ADI adult offspring (GDM: 14.83 ± 0.85a%; GDM + ADI: 11.49 ± 0.58b%; control: 10.03 ± 1.22b%, P = 0.034). Inflammatory markers and oxidative stress were reduced in the adult offspring of AdipoRon-treated mothers. In conclusion, AdipoRon administration to pregnant diabetic rats improved glycaemia in the mothers and long-term glucose tolerance in the offspring. In addition, it tended to reduce excessive foetal fat accumulation and improved n-6/n-3 PUFA ratio significantly in offspring at the adult state.

Intervalos de referencia de ácido úrico en suero durante la gestación / Reference intervals for serum uric acid during pregnancy

Introducción. La interpretación de las magnitudes bioquímicas durante la gestación requiere de intervalos de referencia específicos para dicha etapa, dados los cambios fisiológicos que se producen durante el embarazo. El objetivo de este estudio fue obtener el intervalo de referencia de la concentración sérica de ácido úrico, biomarcador asociado a un incremento del riesgo de desarrollo de preeclampsia en gestantes residentes en el Área 2 de Salud de la Región de Murcia (España). Material y métodos. Estudio prospectivo, longitudinal y consecutivo en el que la población de referencia estuvo finalmente formada por 270 gestantes sanas en las que se midió la uricemia durante los tres trimestres de gestación. Las recomendaciones del Clinical and Laboratory Standards Institute se utilizaron para la obtención de los intervalos de referencia. Resultados. La uricemia aumentó de forma significativa durante la gestación, alcanzando una concentración marcadamente superior durante el tercer trimestre. Se definieron los siguientes intervalos de referencia: primer trimestre: 2,0-4,6 mg/dl, segundo trimestre: 2,0-4,7 mg/dl y tercer trimestre: 2,6-5,7 mg/dl. Conclusión. La interpretación de la uricemia durante la gestación requiere de intervalos de referencia específicos para este estado fisiológico, estratificados por trimestres. Los intervalos obtenidos en nuestro estudio son una herramienta útil en la interpretación de la uricemia durante la gestación para la identificación de aquellas gestantes con un riesgo incrementado de preeclampsia (AU)

Introduction. Interpretation of biochemical variables during pregnancy requires reference intervals specific to that state, due to the physiological changes that occur during pregnancy. The objective of this study was to obtain the reference range of serum uric acid, biomarker associated with an increase in the risk of developing preeclampsia, in pregnant women of the Area 2 of the Region of Murcia (Spain). Material and methods. This is a consecutive longitudinal prospective study in which the reference population finally included 270 healthy pregnant women, in which serum uric acid was measured during the three trimesters of pregnancy. Recommendations of the Clinical and Laboratory Standards Institute were used to obtain reference intervals. Results. Serum uric acid levels increased significantly during pregnancy, reaching a concentration notably higher during the third trimester. The following reference intervals were defined: first trimester: 2,0-4,6 mg/dl, second trimester: 2,0-4,7 mg/dl and third trimester: 2,6-5,7 mg/dl. Conclusion. Interpretation of serum uric acid levels during pregnancy requires reference intervals specific to this physiological state, stratified by trimesters. The ranges obtained in our study are a useful tool to identificate those pregnant women with an increased risk of preeclampsia (AU)