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Long-term effects of maternal diabetes on vascular reactivity and renal function in rat male offspring
Silvia O Rocha1, Guiomar N Gomes, André Luis L Forti
1Department of Physiology, Federal University of São Paulo, Brazil.
Insights
Maternal diabetes during pregnancy can lead to offspring hypertension and reduced kidney function, even without affecting initial nephron number. These changes, linked to impaired Nitric Oxide (NO) vascular response, may accelerate kidney aging.
Area of Science:
- Endocrinology
- Nephrology
- Developmental Biology
Background:
- Fetal growth impairment is a known complication of diabetic pregnancies.
- Long-term effects of maternal diabetes on offspring vascular and renal function are not well understood.
Purpose of the Study:
- To investigate the long-term impact of intrauterine diabetes on the vascular and renal function of offspring.
- To determine if maternal diabetes affects nephron number, glomerular hypertrophy, or blood pressure in offspring.
Main Methods:
- Diabetic rat model induced by streptozotocin (STZ) during gestation.
- Offspring blood pressure, renal function (GFR, RPF), and kidney morphology assessed at various ages.
- Vascular reactivity in mesenteric arteries evaluated in adult offspring.
Main Results:
- Maternal diabetes did not alter offspring nephron number but caused glomerular hypertrophy from 3 months.
- Offspring exhibited decreased Glomerular Filtration Rate (GFR) and Renal Plasma Flow (RPF) from 3 months.
- Hypertension was observed in offspring from 8 weeks, persisting for 12 months, with impaired endothelium-dependent vasodilation.
Conclusions:
- Intrauterine exposure to diabetes induces lasting changes in offspring renal and vascular function.
- Impaired Nitric Oxide (NO)-mediated vasodilation may contribute to accelerated age-related kidney damage in offspring of diabetic mothers.
Abstract:
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.
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