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This Article Full Text Full Text (PDF) All Versions of this Article: 563/1/309    most recent jphysiol.2004.077024v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Thakor, A. S Articles by Giussani, D. A Search for Related Content PubMed PubMed Citation Articles by Thakor, A. S Articles by Giussani, D. A

¹ Department of Physiology, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK

Despite clinical advances in obstetric practice, undiagnosed fetal hypoxaemia still contributes to a high incidence of perinatal morbidity. The fetal defence to hypoxaemia involves a redistribution of blood flow away from peripheral circulations towards essential vascular beds, such as the umbilical, cerebral, myocardial and adrenal circulations. In marked contrast to other essential vascular beds, the mechanisms mediating maintained perfusion of the umbilical circulation during hypoxaemia remain unknown. This study determined the role of calcitonin gene-related peptide (CGRP) in the maintenance of umbilical blood flow during basal and hypoxaemic conditions. Under anaesthesia, five sheep fetuses were instrumented with catheters and a Transonic probe around an umbilical artery, inside the fetal abdomen, at 0.8 of gestation. Five days later, fetuses were subjected to 0.5 h hypoxaemia during either I.V. saline or a selective CGRP antagonist in randomised order. Treatment started 30 min before hypoxaemia and ran continuously until the end of the challenge. The CGRP antagonist did not alter basal blood gas or cardiovascular status in the fetus. A similar fall in P_a,O2 occurred in fetuses during either saline (21 ± 0.8 to 9 ± 0.9 mmHg) or antagonist treatment (20 ± 0.9 to 9 ± 1.2 mmHg). Hypoxaemia during saline led to significant increases in arterial blood pressure, umbilical blood flow and umbilical vascular conductance. In marked contrast, hypoxaemia during CGRP antagonist treatment led to pronounced falls in both umbilical blood flow and umbilical vascular conductance without affecting the magnitude of the hypertensive response. In conclusion, CGRP plays an important role in the umbilical haemodynamic defence response to hypoxaemia in the late gestation fetus.

(Received 7 October 2004; accepted after revision 14 December 2004; first published online 20 December 2004)
Corresponding author D. A. Giussani: Department of Physiology, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK. Email: dag26{at}cam.ac.uk

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