Intrauterine undernutrition: expression and activity of the endothelial nitric oxide synthase in male and female adult offspring.

OBJECTIVE: Epidemiological studies suggest that intrauterine undernutrition plays an important role in the development of arterial hypertension in adulthood. In an attempt to define the mechanisms whereby blood pressure may be raised, we have hypothesized that arteries from offspring of nutritionally restricted dams exhibit abnormalities in the endothelial function and in nitric oxide synthesis. In order to investigate the existence of potential gender differences on the effects of intrauterine undernutrition, both male and female offspring of pregnant Wistar rats on normal and restricted diets were studied in adulthood. METHODS: Female pregnant Wistar rats were fed either normal or 50% of the normal intake diets, during the whole gestational period. At 14 weeks of age, the rats were used for the study of vascular reactivity, eNOS and iNOS gene expression, eNOS activity and, in the case of females, estrogen levels. RESULTS: Intrauterine undernutrition induced hypertension in both male and female offspring, but hypertension was more severe in male rats. Endothelium-intact aortic rings from male and female rats in the restricted diet group exhibited increased responses to norepinephrine, decreased vasodilation to acetylcholine and unaltered responses to sodium nitroprusside in comparison to aortic rings from control rats. No gender-related differences were observed in the vascular reactivity studies. Intrauterine undernutrition promoted decreased gene expression for eNOS in aorta isolated from male, but not female, offspring, reduction in eNOS activity in both male and female offspring and impairment in synthesis of estrogen in female offspring. CONCLUSION: Our data show that intrauterine undernutrition: (1) induces hypertension both in the male and female offspring, hypertension being more severe in male than in female rats; (2) alters endothelium-dependent responses in aortas from the resulting offspring. The endothelial dysfunction is associated with a decrease in activity/expression of eNOS in aortas from male offspring. The mechanism involved in altered response to ACh in female offspring might be a consequence of reduction in estrogen levels leading to reduced eNOS activity.

Severe nutritional restriction in pregnant rats aggravates hypertension, altered vascular reactivity, and renal development in spontaneously hypertensive rats offspring.

Epidemiologic studies suggest that intrauterine undernutrition plays an important role in the development of arterial hypertension in adulthood. The aim of the current study was to evaluate whether severe nutritional restriction during pregnancy can aggravate hypertension, vascular reactivity changes, and renal development in spontaneously hypertensive rat (SHR) offspring. To investigate the potential existence of gender differences, both male and female offspring of pregnant SHRs on a restricted diet were studied in adulthood. Female pregnant SHRs were fed either normal or 50% of the normal intake diets, during the whole gestational period. Arterial blood pressure and nephron number were determined. Norepinephrine, acetylcholine, and sodium nitroprusside responses in isolated aortic rings from the offspring (male and female, when they reached adulthood) were also evaluated. In the SHR offspring (male and female) the intrauterine undernutrition further increased the blood pressure levels, increased the response to norepinephrine, and decreased the response to acetylcholine, without altering the response to sodium nitroprusside. In addition, it induced a decrease in the number of nephrons in the kidney from adult offspring. In conclusion, fetal undernutrition aggravates hypertension and the endothelial dysfunction along with an impairment of renal development in both male and female SHRs.