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Cardiovascular, metabolic and endocrine effects of chemical sympathectomy and of adrenal demedullation in fetal sheep.

A procedure in fetal sheep for causing peripheral sympathectomy by regular intravascular guanethidine sulphate administration and for causing adrenal demedullation by intragland injection of acid formalin is reported. Demedullation substantially removed adrenaline from the fetal circulation, but has a small effect only on noradrenaline. Plasma noradrenaline levels were depressed by 50% when demedullated fetuses were also subject to peripheral sympathectomy by guanethidine sulphate treatment. This provides some evidence that the paraganglia in the sheep fetus contributes to resting plasma catecholamines. Furthermore the ability of adrenal demedullation to increase markedly this pool of extra-adrenal chromaffin tissue indicates that in the fetus adrenal activity regulates the growth of these para-aortic bodies. In response to sympathectomy plasma vasopressin concentrations rose substantially, whilst adrenal demedullation caused a small rise. Demedullation and sympathectomy depressed fetal plasma glucose and elevated plasma cortisol. In both sympathectomised and adrenal demedullated fetuses resting heart rate and blood pressure was not depressed. However in those with a depleted peripheral nervous system periods of cardiovascular instability were apparent after 2-3 days of treatment with guanethidine sulphate. Hence there were regular episodes where fetal blood pressure and heart rate fell sharply followed 60-90s later by very large increases in blood pressure sustained for up to 10 min and associated with substantial production of plasma vasopressin and catecholamines. These results show that fine cardiovascular control in the fetus requires an intact sympathetic system as the endocrine system is too slow responding to effectively maintain reflex vascular control.