PRENATAL PROGRAMMING AND ARTERIAL HYPERTENSION IN COMMON MARMOSET MONKEYS

C Schlumbohm1, C Bramlage2, B Egner3, E Fuchs1. 1) German Primate Center, Göttingen, Germany; 2) Faculty of Medicine, Georg-August-University, Göttingen, Germany, 3) Dr. Egner Clinical Research and Continued Education, Mainhausen, Germany.

C.Schlumbohm, German Primate Center, Göttingen, 2006

Epidemiological studies in humans have shown that low birth weight is associated with increased prevalence of hypertension, obesity and metabolic syndrome in later life (1). In experimental studies with rodents and sheep it could be demonstrated that prenatal stress either from maternal calorie or protein restriction or from maternal treatment with synthetic glucocorticoids induced low birth weight, hypertension and/or obesity in the offspring. It is hypothesized that in humans and possibly also in other species hypertension and metabolic disorders have their origin in fetal life. It is not clear, however, whether prenatal exposition to glucocorticoids would have adverse effects on body mass or blood pressure also in other species, such as non-human primates.

We therefore investigated common marmoset monkeys, a small (350 to 450 g bodyweight) South American non-human primate species. Two groups of pregnant common marmosets were treated orally either during early (“eDEX”; 42-48 days post conceptionem (p.c.).: N=15) or during late pregnancy “lDEX”; 90-96 days p.c.: N=15) with 5mg dexamethasone (DEX) per kg maternal body weight per day. A control group (con) of 15 pregnant marmosets received vehicle only. In male offspring urine and serum samples were collected and blood pressure was measured oscillometrically (MD-Scientific 1500, S+B medVET, Babenhausen, Germany). The oscillometric unit showed high correlation and accuracy compared to direct blood pressure recordings.

Prenatal DEX had no effect on birth weight of male marmosets (con: 31.0±3.7g; eDEX: 30.2± 2.4g; lDEX: 30.6 ± 3.7g; mean ± SD) and on body weight at day 320 of age (con: 350 ± 50g; eDEX:323 ± 40g; lDEX:354 ± 53g ; mean ± SD). Systolic blood pressure was significantly higher in lDEX compared to eDEX (p<0.05, one way ANOVA, Holm-Sidak test) but did not differ from controls (con: 148 ± 9; eDEX:140 ± 16; lDEX:159 ± 23 mm Hg ; mean ± SD). No effect of prenatal DEX was observed on diastolic blood pressure (con: 73 ± 13; eDEX: 68 ± 11; lDEX:79 ±17 mm Hg; mean ± SD). Urinary aldosterone was significantly (p<0.05) elevated in lDEX compared to eDEX and to controls (con:89±14; eDEX:99±20; lDEX:171±28ng/ml; mean ± SEM).
   In contrast to findings in rodents prenatal treatment with DEX had no influence on bodyweight in marmoset monkeys. Elevated blood pressure and increased urinary aldosterone in lDEX adolescent marmosets supports the hypothesis that prenatal DEX may program fetal tissues for hypertension in later life presumably by involvement of the renin-angiotensin-aldosterone system (RAAS). Supported by the European Commission grant QLRT-2001-02758 (EUPEAH).

1) Edwards LJ et al., Clin Exp Pharm Phys 28: 938-941, 2001.