The reliance on α‐adrenergic receptor stimuli for blood pressure regulation in the chronically hypoxaemic fetus is not dependent on post‐ganglionic activation

• Published in: The Journal of physiology 2021-02, Vol.599 (4), p.1307-1318
• Main Authors: Darby, Jack R. T., Varcoe, Tamara J., Holman, Stacey L., McMillen, I. Caroline, Morrison, Janna L.
• Format: Article
• Language: English
• Subjects: Adrenergic receptors; Animals; Blood Pressure; cardiovascular; Cardiovascular diseases; Catheterization; chronic hypoxaemia; Female; Fetal Growth Retardation; Fetus; Fetuses; Gestational age; Hypoxia; Norepinephrine; Placenta; placental insufficiency; Pregnancy; Receptors, Adrenergic, alpha; Sheep; Surgery; sympathetic nervous system
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/JP280693

Key points Chronic hypoxaemia is associated with intrauterine growth restriction (IUGR) and a predisposition to the development of hypertension in adult life. IUGR fetuses exhibit a greater reliance on α‐adrenergic activation for blood pressure regulation. The fetal blood pressure response to post‐ganglionic blockade is not different between control and IUGR fetuses. The decrease in mean arterial pressure is greater in the IUGR sheep fetus after α‐adrenergic receptor blockade at the level of the vasculature and this is inversely related to fetal PO2. The increased reliance that the IUGR fetus has on α‐adrenergic activation for maintenance of mean arterial pressure is not a result of increased post‐ganglionic sympathetic activation. Intrauterine growth restriction (IUGR) is associated with an increased risk of cardiovascular disease in adult life. Placental restriction (PR) in sheep results in chronic hypoxaemia and early onset IUGR with increased circulating plasma noradrenaline concentrations. These IUGR fetuses exhibit a greater decrease in mean arterial pressure (MAP) during α‐adrenergic blockade. We aimed to determine the role of post‐ganglionic sympathetic activation with respect to regulating MAP in IUGR fetal sheep. PR was induced by carunclectomy surgery prior to conception. Fetal vascular catheterization was performed at 110–126 days gestational age (GA) (term, 150 days) in nine control and seven PR‐IUGR fetuses. The fetal blood pressure response to both a post‐ganglionic and an α‐adrenergic receptor blocker was assessed at 116–120 days GA and/or 129–131 days GA. The effect of both post ganglionic and α‐adrenergic blockade on fetal blood pressure was then compared between control and IUGR fetuses at both GAs. There was no difference in the effect of post‐ganglionic blockade on MAP in control and IUGR fetal sheep at either 116–120 days GA or 129–131 days GA. α‐adrenergic receptor blockade decreased MAP to the same extent in both control and IUGR fetuses at 116–120 days GA. At 129–131 days GA, the drop in MAP in response to α‐adrenergic receptor blockade was greater in IUGR fetuses than controls. There was a significant inverse relationship between the drop in MAP in response to α‐adrenergic receptor blockade at both GAs with fetal PO2. Thus, the increased dependence on α‐adrenergic activation for blood pressure regulation in the chronically hypoxaemic IUGR fetus is not a result of increased post‐ganglionic sympathetic activation. Key points Chronic