Altered cardiovascular haemodynamics and baroreceptor-heart rate reflex inadult sheep after prenatal exposure to dexamethasone

Numerous epidemiological studies, together with mounting evidence from stud ies in animals, point to a correlation between an adverse intrauterine envi ronment and the early onset of cardiovascular and metabolic diseases later in life. We were the first to show that sheep exposed to dexamethasone (0.2 8 mg.kg(-1).day(-1) for only 2 days) at the end of the first month of pregn ancy (PTG1), but not those exposed at the end of the second month of pregna ncy (PTG2), had a higher basal mean arterial pressure (MAP) 19 months after birth. In the present study we report the MAP, cardiovascular haemodynamic s and baroreflex sensitivity in these animals at 40 months of age. MAP in t he PTG1 group was significantly higher than in the control group (91 +/- 1 mmHg and 81 +/- mmHg respectively; P < 0.001) and also when compared with t he PTG2 group (82 +/- 1 mmHg; P < 0.001). There was a significant increase in cardiac output in the PTG1 group com pared 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).b eat(-1) in the control group; P < 0.05), but not in heart rate. In the hype rtensive group of animals (PTG1), there was a rightward shift of the barore flex 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, sugges ting an impairment in the central processing of the baroreceptor signals. T h us sheep fetuses exposed to dexamethasone for only 2 days at the end of t he first month of gestation have high blood pressure (dependent upon the in crease 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 baror eceptor-heart rate response.