Elevated blood pressure in high fat diet-exposed low birth weight rat offspring is most likely caused by elevated glucocorticoid levels

Abstract

Being delivered as a low birthweight (LBW) infant is a risk factor for elevated blood pressure and future problems with cardiovascular and cerebellar diseases. Premature babies have been reported to possess a lower number of nephrons, but the mechanisms by which blood pressure is elevated in full-term LBW infants remain unclear. We generated a fetal low-carbohydrate and calorie-restricted model rat, and some individuals showed postnatal growth failure caused by increased miR-322 expression in the liver and decreased growth hormone receptor expression. Using this model, we examined how a high-fat diet-induced mismatch between prenatal and postnatal environments could elevate blood pressure after growth. Although LBW rats fed standard chow had slightly higher blood pressure than control rats, their blood pressure was significantly higher than controls when exposed to a high-fat diet. Observation of glomeruli subjected to PAM staining showed no difference in number or size. Aortic and cardiac angiotensin II receptor expression was altered with compensatory responses. Blood aldosterone levels were not different between control and LBW rats, but blood corticosterone levels were significantly higher in the latter with high-fat diet exposure. Administration of metyrapone, a steroid synthesis inhibitor, reduced blood pressure to levels comparable to controls. We showed that high-fat diet exposure causes impairment of the pituitary glucocorticoid feedback via miR-449a. These results clarify that LBW rats have increased blood pressure due to high glucocorticoid levels when they are exposed to a high-fat diet. These findings suggest a new therapeutic target for hypertension of LBW individuals.