IMPACT OF PLACENTAL RESTRICTION ON THE DEVELOPMENT OF THE SYMPATHOADRENAL SYSTEM

We have investigated the impact of chronic restriction of placental fu nction on circulating catecholamine concentrations and responses to th e indirectly acting, sympathomimetic amine, tyramine, in the fetal she ep in late gestation. In 10 ewes, endometrial caruncles or placental p lacentation sites were removed before conception (placental restrictio n (PR) group). Fetal sheep in the PR group were hypoxemic throughout l ate gestation and growth-restricted (3.02 +/- 0.35 kg) when compared w ith control fetal sheep (4.30 +/- 0.29 kg; n = 8) at 140 d of gestatio n. Fetal plasma concentrations of noradrenaline and adrenaline were hi gher (p < 0.05) in the PR (7.06 +/- 3.17 pmol/mL and 2.89 +/- 2.01 pmo l/mL, respectively) than in the control group (3.55 +/- 0.54 pmol/mL a nd 1.30 +/- 0.48 pmol/mL, respectively) throughout late gestation. Pla sma noradrenaline, but not adrenaline concentrations, increased signif icantly between 110 and 140 d of gestation in both the PR and control group, and there was a significant inverse relationship between plasma noradrenaline and arterial Po, in the PR and control groups (plasma n oradrenaline = 12.34 - 0.40 Po-2). In the PR group, plasma noradrenali ne increased (p < 0.05) after tyramine infusion from 4.51 +/- 1.28 pmo l/mL to a peak of 19.40 +/- 3.56 pmol/mL. In the control group, noradr enaline increased from 2.08 +/- 0.30 pmol/mL to a peak of 12.23 +/- 1. 67 pmol/mL after tyramine infusion. There was no difference, however, in the maximal proportional changes in plasma noradrenaline concentrat ions in the PR (319 +/- 55%) and control (449 +/- 100%) groups after t yramine. We conclude that the most likely source of the increased plas ma catecholamines in the PR group is enhanced catecholamine synthesis and secretion from developing sympathetic neurons.