Long term effects of fetal undernutrition on rat heart. Role of hypertension and oxidative stress

Abstract

Background and aimsFetal undernutrition is a risk factor for heart disease in both genders, despite the protection of women against hypertension development. Using a rat model of maternal undernutrition (MUN) we aimed to assess possible sex differences in the development of cardiac alterations and the implication of hypertension and cardiac oxidative stress.MethodsMale and female offspring from rats fed ad libitum (control) or with 50% of the normal daily intake during the second half of gestation (MUN) were used. Heart weight/body weight ratio (HW/BW), hemodynamic parameters (anaesthetized rats) and plasma brain natriuretic peptide (BNP, ELISA) were assessed in 21-day, 6-month and 22-month old rats. Plasma testosterone (ELISA) and cardiac protein expression of enzymes related to reactive oxygen species synthesis (p22phox, xanthine-oxidase) and degradation (catalase, Cu/Zn-SOD, Mn-SOD, Ec-SOD) were evaluated in 21-day and 6-month old rats (Western Blot). Heart structure and function was studied at the age of 22 months (echocardiography).ResultsAt the age of 21 days MUN males exhibited significantly larger HW/BW and cardiac p22phox expression while females had reduced p22phox expression, compared to their respective sex-matched controls. At the age of 6-months, MUN males showed significantly larger blood pressure and cardiac xanthine-oxidase expression; MUN females were normotensive and had a lower cardiac expression of antioxidant enzymes, compared to their respective sex-matched controls. At the age of 22 months, both MUN males and females showed larger HW/BW and left ventricular mass and lower ejection fraction compared to sex-matched controls; only MUN males exhibited hypertension and a larger plasma BNP compared to aged male controls.Conclusions1) During perinatal life females exposed to fetal undernutrition are protected from cardiac alterations, but in ageing they exhibit ventricular hypertrophy and functional loss, like MUN males; 2) cardiac oxidative stress might be implicated in the observed heart alterations in both sexes and 3) the severity of cardiac damage might be greater in males due to hypertension.

Role of fetal nutrient restriction and postnatal catch‐up growth on structural and mechanical alterations of rat aorta

“…These data confirm the sexual differences in blood pressure development in rats exposed to global nutrient restriction during fetal life, as has been previously described by others and by us (Dasinger & Alexander, ; Rodríguez‐Rodríguez et al . ). We analysed blood pressure under medetomidine/ketamine anaesthesia, which needs to be taken into consideration since both drugs exert cardiovascular effects.…”

“…In fact, we have evidence of a lower HR in MUN and Control rats under medetomidine/ketamine anaesthesia compared to diazepam/ketamine (Rodríguez‐Rodríguez et al . ). Under our experimental conditions, using a mixture of both anaesthetics, we observed an initial pressure drop that stabilized after 30 min.…”

“…) and the heart (Rodríguez‐Rodríguez et al . ). Vascular remodelling in the aorta was not accompanied by increased vessel stiffness in early life.…”

“…To test this hypothesis we have used a rat model of fetal nutrient restriction induced by maternal undernutrition during gestation (MUN), in which only male offspring develop hypertension (Rodríguez‐Rodríguez et al . , ). We have established two experimental groups (MUN and Control) and compared the following variables in both male and female animals at three age points (birth, weaning period and adult life).…”

Handling has an anxiolytic effect that is not affected by the inhibition of the protein kinase C pathway in adult prenatal undernourished male rat offspring

“…*P < 0.05, **P < 0.01, ***P < 0.001 significant differences in body weight were observed by 3 weeks of age. [26][27][28] Low birth weights were recovered by 7 weeks of age even when maternal rats were fed 40% of that provided for control pregnant rats throughout pregnancy. 29 These reports suggest that the effects of food restriction during pregnancy on body weights of offspring are generally observed during the juvenile period, and normal body weights are restored by adulthood.…”