Peri-Implantation Undernutrition Programs Blunted Angiotensin II Evoked Baroreflex Responses in Young Adult Sheep

Abstract

Abstract-An adverse environment around conception and implantation influences later fetal growth and development to term in humans and sheep. Indeed, preimplantation undernutrition of rats elevated the systolic blood pressure of the resultant adult offspring. In this study, adult cardiovascular function is examined in a slower growing, non-litter-bearing species after peri-implantation undernutrition. Eight ewes were fed to 50% equivalent food intake of 12 control ewes from 1 to 30 days (term Ϸ147 days) only. Following consumption of an adequate diet to term, natural lambing, and then weaning, resting cardiovascular status and baroreflex function were examined in the resultant young adult offspring. Birth weight and postnatal growth to 1 year of age were unaffected by early undernutrition; however, nutrient-restricted sheep had increased pulse pressure, a reduced rate pressure product, and a leftward shift in their baroreflex function curve. Baroreflex sensitivity during angiotensin II infusion was also blunted in early nutrient-restricted sheep but the tachycardia following a reduction in central blood pressure appeared potentiated, relative to controls. The data suggest that peri-implantation undernutrition may program long-term cardiovascular dysfunction that ultimately increases the risk of hypertension later in life. An increase in regional angiotensin II activity during this critical early phase of development is a likely candidate mechanism for the effects observed. The data have broad implications for the health outcome of those offspring from mothers who were poorly nourished during early, often unknown pregnancy and for embryos artificially manipulated because of infertility treatment. Key Words: sheep Ⅲ angiotensin II Ⅲ blood pressure Ⅲ baroreflex H ypertension is a major risk factor associated with coronary heart disease and represents a common cause of death in the population more than 50 years old. 1 Hypertension and coronary heart disease are both multifactorial in their etiology but epidemiological studies in a number of different human populations have shown that the prenatal environment has an important role in determining the incidence of these diseases. 2 Consequently, there has been renewed interest in the effect of poor gestational nutrition on pre-and postnatal growth after the early studies of McCance and Widdowson. 3,4 These original hypotheses have been advanced to include changes in physiological function leading to adult pathology-the "developmental origins of adult disease hypothesis." 5,6 The methodologies and inferences of the hypothesis have been criticized 7,8 but meta-analyses have illustrated the strength of the epidemiological findings. 1,9 Work from the many animal models that now exist strongly supports the hypothesis and suggests that programming of disease risk is both biologically plausible and of major importance in terms of public health. 5,10

Effect of periconceptional undernutrition and gender on hypothalamic–pituitary–adrenal axis function in young adult sheep

“…Details of maternal weight gain/loss during the period of undernutrition are as described previously (Gardner et al 2004). Plasma concentrations of maternal cortisol were similar on days 2 and 30 of gestation in both control and NR ewes, and for clarity these data are presented in Fig.…”

“…(3) To separate pituitary from adrenal responsiveness we also, on a different day, administered a separate bolus dose of synthetic ACTH. Given the cardiopressor actions of AVP in high concentrations (Cowley 1988) and that periconceptional undernutrition has been shown to influence blood pressure regulation (Gardner et al 2004), then the fourth aim of the study was to examine the cardiovascular responses to a CRH and AVP bolus.…”

DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status

“…Carotid and jugular catheters were inserted into each animal under general anesthesia, and animals were allowed 2 days of postoperative recovery before the commencement of procedures. Resting and stimulated cardiophysiology were determined on the third day (31). After a period of stabilization (typically lasting 30 min), resting systolic, diastolic, and mean arterial blood pressure and heart rate were measured (at 1-sec intervals) during the course of a further 30 min by precalibrated pressure transducers (SensorNor 840, S 4925; Horten) linked to a data-acquisition system (Po-Ne-Mahphysiology platform, Model P3P; Linton Instruments).…”

The relationship between birth weight and pulse pressure in children: cross-sectional study

“…In utero nutrient restricted young adult sheep have also been shown to have increased pulse pressure, although their birth weights were unaffected. 24 In what appears to be the only previous study of birth weight and pulse pressure in childhood, Lurbe et al 14 observed that birth weight was inversely related to ambulatory pulse pressure in a study of a 300 healthy children aged between 10 and 18 years. Although our results are consistent with those of Lurbe et al 14 further analysis demonstrated that the relationship was restricted to the girls in our cohort.…”