A putative role for hypothalamic glucocorticoid receptors in hypertension induced by prenatal undernutrition in the rat.
Prenatal undernutrition induces hypertension later in life, possibly by disturbing the hypothalamo-pituitary-adrenal axis through programming decreased expression of hypothalamic glucocorticoid receptors. We examined the systolic blood pressure, heart rate and plasma corticosterone response to intra-paraventricular dexamethasone, mifepristone and corticosterone in eutrophic and prenatally undernourished young rats. Undernutrition was induced during fetal life by restricting the diet of pregnant mothers to 10 g daily (40% of diet consumed by well-nourished controls). At day 40 of postnatal life (i) intra-paraventricular administration of dexamethasone significantly reduced at least for 24h both the systolic pressure (-11.6%), the heart rate (-20.8%) and the plasma corticosterone (-40.0%) in normal animals, while producing lower effects (-5.5, -8.7, and -22.3%, respectively) on undernourished rats; (ii) intra-paraventricular administration of the antiglucocorticoid receptor ligand mifepristone to normal rats produced opposite effects (8.2, 20.3, and 48.0% increase, respectively) to those induced by dexamethasone, being these not significant in undernourished animals; (iii) intra-paraventricular corticosterone did not exert any significant effect. Results suggest that the low sensitivity of paraventricular neurons to glucocorticoid receptor ligands observed in prenatally undernourished rats could be due to the already reported glucocorticoid receptor expression, found in the hypothalamus of undernourished animals.
Pérez
Hernán
H
Laboratory of Nutrition and Metabolic Regulation, Institute of Nutrition and Food Technology, University of Chile, Santiago, Chile. hperez@inta.cl
Soto-Moyano
Rubén
R
Ruiz
Samuel
S
Hernández
Alejandro
A
Sierralta
Walter
W
Olivares
Ricardo
R
Núñez
Héctor
H
Flores
Osvaldo
O
Morgan
Carlos
C
Valladares
Luis
L
Gatica
Arnaldo
A
Flores
Francisco J
FJ
D000818:Animals; D019540:Area Under Curve; D003345:Corticosterone / Q000097:blood; D005260:Female; D006339:Heart Rate / Q000502:physiology; D006973:Hypertension / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000503:physiopathology; D007031:Hypothalamus / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D044342:Malnutrition / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000378:metabolism / Q000503:physiopathology; D011247:Pregnancy; D039401:Prenatal Nutritional Physiological Phenomena / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000378:metabolism*
D011965:Receptors, Glucocorticoid; D003345:Corticosterone