ABSENCE OF TRANSSYNAPTIC BETA ADRENERGIC RECEPTOR REGULATION IN OVINE FETAL LUNG AND HEART:

We examined the effect of altered transsynaptic neural activity on lung and heart BAR development in the ovine fetus following chemical sympathectomy (CS) with guanethidine sulfate (GS). CS was induced by chronic administration of GS using subcutaneously implanted miniosmotic infusion pumps programmed to deliver 17 mg/kg/day for 14 days (4 animals). Control fetuses were infused with vehicle alone (4 animals). Animals were delivered by cesarean section. The extent of sympathetic denervation was assessed by measurement of tissue norepinephrine (NE) content using a sensitive, specific radioenzymatic assay. BAR concentration and affinity were measured using the tritiated radioligand dihydroalprenolol (DHA). Lung NE was unchanged following CS while cardiac atrial NE was 10% of control (p<.001) and ventricular NE was 19% of control values (p<.001). Lung and ventricular BAR were 112 and 100% of control values, respectively (p>0.05). Brown adipose tissue NE and adrenal catecholamine (CAT) concentrations were unchanged by CS. Conclusions: 1) GS at the dosage utilized causes extensive atrial and ventricular sympathetic denervation but does not affect lung, BAT or adrenal CAT contents. 2) Sympathetic denervation of the developing ventricle is not associated with up-regulation of BAR. Speculation: Myocardial BAR development in fetal life is not subject to the “normal” postpartum transsynaptic regulatory influences.