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

被引:75
作者
Dodic, M [1 ]
Peers, A
Coghlan, JP
May, CN
Lumbers, E
Yu, ZY
Wintour, EM
机构
[1] Univ Melbourne, Howard Florey Inst Expt Physiol & Med, Parkville, Vic 3052, Australia
[2] Univ Melbourne, Dept Anat & Cell Biol, Parkville, Vic 3052, Australia
[3] Univ New S Wales, Sch Physiol & Pharmacol, Sydney, NSW 2052, Australia
关键词
dexamethasone; hypertension; sheep;
D O I
10.1042/CS19980356
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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 +/- 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 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).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. Th us 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.
引用
收藏
页码:103 / 109
页数:7
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