Altered cardiovascular haemodynamics and baroreceptor–heart rate reflex in adult sheep after prenatal exposure to dexamethasone

Abstract

Numerous epidemiological studies, together with mounting evidence from studies in animals, point to a correlation between an adverse intrauterine environment and the early onset of cardiovascular and metabolic diseases later in life. We were the first to show that sheep exposed to dexamethasone (0.28 mg⋅kg-1⋅day-1 for only 2 days) at the end of the first month of pregnancy (PTG1), but not those exposed at the end of the second month of pregnancy (PTG2), had a higher basal mean arterial pressure (MAP) 19 months after birth. In the present study we report the MAP, cardiovascular haemodynamics and baroreflex sensitivity in these animals at 40 months of age. MAP in the PTG1 group was significantly higher than in the control group (91±1 mmHg and 81±1 mmHg respectively; P< 0.001) and also when compared with the PTG2 group (82±1 mmHg; P< 0.001). There was a significant increase in cardiac output in the PTG1 group compared with the control group (108±2 and 96±4 ml⋅min-1⋅kg-1 respectively; P< 0.05). The increase in cardiac output in the PTG1 group was due to an increase in stroke volume (1.82±0.08 ml⋅kg-1⋅beat-1, compared with 1.46±0.06 ml⋅kg-1⋅beat-1 in the control group; P< 0.05), but not in heart rate. In the hypertensive group of animals (PTG1), there was a rightward shift of the baroreflex curve. In group PTG2 (the normotensive group of animals), a lower gain was found before and during propranolol treatment. The decrease in gain of the baroreflex was not associated with changes in heart rate range, suggesting an impairment in the central processing of the baroreceptor signals. Thus sheep fetuses exposed to dexamethasone for only 2 days at the end of the first month of gestation have high blood pressure (dependent upon the increase in cardiac output) and a reset of the baroreflex at 40 months of age. Animals that have received prenatal dexamethasone closer to mid-gestation, although normotensive with normal cardiac output, showed an altered baroreceptor-heart rate response.