Adrenergic and vasopressinergic contributions to the cardiovascular response to acute hypoxaemia in the llama fetus

Abstract

The effects of fetal intravenous treatment with phentolamine or a vasopressinergic V1‐receptor antagonist on the fetal cardiovascular responses to acute hypoxaemia in the llama were investigated. Six llama fetuses were surgically prepared between 60 and 70% of gestation under general halothane anaesthesia with vascular catheters and transit‐time ultrasonic flow probes around a carotid artery and a femoral artery. At least 4 days after surgery all fetuses were subjected to a 3 h experiment: 1 h of normoxia, 1 h of hypoxaemia and 1 h of recovery while on slow i.v. infusion with saline. On separate days this experiment was repeated with fetal i.v. treatment with either phentolamine or a V1‐receptor antagonist dissolved in saline. During saline infusion all llama fetuses responded to acute hypoxaemia with intense femoral vasoconstriction. Phentolamine during normoxia produced hypotension, tachycardia and vasodilatation in both the carotid and the femoral circulations. During hypoxaemia, fetuses treated with phentolamine did not elicit the pronounced femoral vasoconstriction and all died within 20 min of the onset of hypoxaemia. A V1‐receptor antagonist produced a femoral vasodilatation during normoxia but did not affect the fetal cardiovascular responses to acute hypoxaemia. In conclusion, α‐adrenergic and V1‐vasopressinergic mechanisms contribute to a basal vasoconstrictor tone in the femoral circulation in the llama fetus. The enhanced femoral vasoconstriction during acute hypoxaemia in the llama fetus is not mediated by stimulation of V1‐vasopressin receptors, but is dependent on α‐adrenergic receptor stimulation. Such α‐adrenergic efferent mechanisms are indispensable to fetal survival during hypoxaemia in the llama since their abolition leads to cardiovascular collapse and death.

Chronic Hypoxia Stimulates Periarterial Sympathetic Nerve Development in Chicken Embryo

“…Though the mechanism behind this enhanced ␣-adrenergic response is not yet known, increased peripheral sympathetic innervation may play a role. 6 Despite biochemical and histological signs of sympathetic hyperinnervation, the adrenergic vasoconstrictor responsiveness of chicken embryo femoral arteries was not reduced after chronic hypoxia. Arterial sensitivity to exogenous NE was normalized when neuronal reuptake of NE was pharmacologically blocked with cocaine.…”

“…5,6 Direct hypoxia-induced release of adrenal catecholamines (CA) participates in this acute fetal cardiovascular response. Prolonged periods of hypoxia may stimulate the expression of tyrosine hydroxylase (TH), the rate-limiting step in CA synthesis, 7 as has also been shown in adult animals.…”

Direct effects of acute hypoxia on the reactivity of peripheral arteries of the chicken embryo

“…5 illustrates that our in vitro findings might be relevant for the hemodynamics in prenatal life in vivo. In the mammalian fetus, an acute decrease in oxygen results in cardiovascular responses involving an elevation in blood pressure and redistribution of the cardiac output mediated by increased levels of circulating catecholamines (9,10), which are released from the adrenals and later in gestation from the sympathetic nerves (38). During acute hypoxia, NE levels rise from 0.1 M up to 0.8 M in the chicken embryo (24).…”

“…Later in gestation, activation of efferent sympathetic nerves also contributes to the response (38). Antagonists of ␣-adrenoreceptors blunt the hypoxia-induced increase in fetal total peripheral resistance (9,10,25).…”

“…In fetal lambs (10), fetal llamas (9), and chicken embryos (24,25), increased levels of circulating catecholamines take part in this response. Early in gestation, the chromaffin cells in the primitive adrenal medulla are directly sensitive to low oxygen tension.…”