Xanthine oxidase and the fetal cardiovascular defence to hypoxia in late gestation ovine pregnancy.

Hypoxia is a common challenge to the fetus, promoting a physiological defence to redistribute blood flow towards the brain and away from peripheral circulations. During acute hypoxia, reactive oxygen species (ROS) interact with nitric oxide (NO) to provide an oxidant tone. This contributes to the mechanisms redistributing the fetal cardiac output, although the source of ROS is unknown. Here, we investigated whether ROS derived from xanthine oxidase (XO) contribute to the fetal peripheral vasoconstrictor response to hypoxia via interaction with NO-dependent mechanisms. Pregnant ewes and their fetuses were surgically prepared for long-term recording at 118 days of gestation (term approximately 145 days). After 5 days of recovery, mothers were infused i.v. for 30 min with either vehicle (n = 11), low dose (30 mg kg(-1), n = 5) or high dose (150 mg kg(-1), n = 9) allopurinol, or high dose allopurinol with fetal NO blockade (n = 6). Following allopurinol treatment, fetal hypoxia was induced by reducing maternal inspired O2 such that fetal basal P aO 2 decreased approximately by 50% for 30 min. Allopurinol inhibited the increase in fetal plasma uric acid and suppressed the fetal femoral vasoconstrictor, glycaemic and lactate acidaemic responses during hypoxia (all P < 0.05), effects that were restored to control levels with fetal NO blockade. The data provide evidence for the activation of fetal XO in vivo during hypoxia and for XO-derived ROS in contributing to the fetal peripheral vasoconstriction, part of the fetal defence to hypoxia. The data are of significance to the understanding of the physiological control of the fetal cardiovascular system during hypoxic stress. The findings are also of clinical relevance in the context of obstetric trials in which allopurinol is being administered to pregnant women when the fetus shows signs of hypoxic distress.

Effect of arginine vasopressin on regional adrenal blood flow and plasma cortisol concentration in fetal sheep.

OBJECTIVE: To determine whether arginine vasopressin (AVP) at plasma concentrations measured during moderate hypoxemia affects adrenal blood flow. STUDY DESIGN: Regional blood flows were measured in 5 unanesthetized normoxemic fetuses (124-128 days' gestation) during a 24-h intravenous infusion of AVP in isotonic saline solution. Another 5 fetuses received an infusion of vehicle. Blood flows were determined before the infusion and at 2 h and 24 h from its onset using radionuclide-labeled microspheres. RESULTS: At 2 h and 24 h of AVP infusion, fetal plasma concentrations of IR-AVP had risen from 4.7 +/- 0.9 pg/ml to 9.8 +/- 1.1 pg/l and 9.4 +/- 0.7 pg/ml, respectively. Thus we achieved plasma concentrations of IR-AVP comparable to those previously reported during moderate hypoxemia. There was no significant effect of treatment on fetal plasma concentrations of immunoreactive adrenocorticotropic hormone (ACTH) or cortisol. AVP infusion significantly decreased fetal heart rate and raised cotyledonary blood flow from 198 +/- 18 ml/min per 100 g to 235 +/- 17 ml/min and 218 +/- 10 ml/min per 100 g at 2 h and 24 h, respectively, from the start of the AVP infusion. Basal values for adrenal medullary and cortical blood flows were similar in the AVP and saline groups, and did not change significantly during the infusions. CONCLUSION: These findings suggest that the rise in adrenal blood flow seen after hypoxemia is not due to a direct action of systemic AVP, but is attributable to other influences, likely including changes in circulating ACTH.