Green, Lucy Rebecca; (1996) Mechanisms of fetal cardiovascular responses to acute hypoxia. Doctoral thesis (Ph.D.), University College London (United Kingdom).

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Abstract

During acute hypoxia the term fetal sheep redistributes its combined ventricular output favouring the heart, brain and adrenal glands, at the expense of peripheral vascular beds. Regional changes in organ blood flow are likely to affect their function and growth. The redistribution is characterised by an initial bradycardia, a rapid and sustained fall in peripheral blood flow and a slower rise in mean arterial pressure. There is a large carotid chemoreceptor (CCR) component to the rapid cardiovascular changes, with a-adrenergic and muscarinic efferent limbs to the periphery and heart, respectively. Catecholamine release contributes to these responses, but there is reason to suggest the involvement of other reflexly released humoral agents, e.g. angiotensin II (AII). In addition hypoxia may act at a local tissue level, in particular on the vascular endothelium, in the control of systemic vascular tone. Renal blood flow (RBF) and urine output (UO) fall during hypoxia however it is not known whether RBF changes determine UO changes, or indeed the role played by CCRs. In chronically instrumented sheep model I have firstly examined the role of CCRs in blood flow distribution in relation to organ function by correlating RBF and UO during hypoxia. Secondly, I have investigated the role of All in cardiovascular responses to acute hypoxia using an angiotensin converting enzyme inhibitor, captopril, in intact fetuses and those which had been carotid sinus denervated (CSD) to remove carotid chemoreflexes. Thirdly, I have blocked endothelin-1 (ET-1) type A receptors and specifically inhibited nitric oxide synthase (NOS) to investigate the role of ET-1 and nitric oxide (NO), respectively, in cardiovascular control during normoxia and hypoxia. Finally I have investigated the role of NO in the development of fetal cardiovascular tone using chronically infused NOS-inhibitor. My results suggest that: 1) A component of the initial fall in RBF during hypoxia is a carotid chemoreflex. Changes in RBF are not a major determinant of UO; 2) All concentration rises during hypoxia but is not chemoreflexly released, although All may play a greater role in vasoconstriction in CSD fetuses; 3) ET-1 and NO modulate vascular resistance and FHR during normoxia and hypoxia, and NO mediates the rise in carotid blood flow in hypoxia; 4) Preliminary results implicate a role for NOS in peripheral vascular development.

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