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This Article Full Text Full Text (PDF) All Versions of this Article: 566/2/587    most recent jphysiol.2005.085431v1 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 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

² Faculty of Medicine, Imperial College, Hammersmith Hospital, London W12 ONN, UK

The fetal defence to acute hypoxaemia involves cardiovascular and metabolic responses, which include peripheral vasoconstriction and hyperglycaemia. Both these responses are mediated via neuroendocrine mechanisms, which require the stimulation of the sympathetic nervous system. In the adult, accumulating evidence supports a role for calcitonin gene-related peptide (CGRP) in the activation of sympathetic outflow. However, the role of CGRP in stimulated cardiovascular and metabolic functions before birth is completely unknown. This study tested the hypothesis that CGRP plays a role in the fetal cardiovascular and metabolic defence responses to acute hypoxaemia by affecting sympathetic outflow. Under anaesthesia, five sheep fetuses at 0.8 of gestation were surgically instrumented with catheters and a femoral arterial Transonic flow-probe. 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. Arterial samples were taken for blood gases, metabolic status and hormone analyses. CGRP antagonism did not alter basal arterial blood gas, metabolic, cardiovascular or endocrine status. During hypoxaemia, similar falls in P_a,O2 occurred in all fetuses. During saline infusion, hypoxaemia induced hypertension, bradycardia, femoral vasoconstriction, hyperglycaemia and an increase in haemoglobin, catecholamines and neuropeptide Y (NPY). In contrast, CGRP antagonism markedly diminished the femoral vasoconstrictor and glycaemic responses to hypoxaemia, and attenuated the increases in haemoglobin, catecholamines and NPY. Combined, these results strongly support the hypothesis that CGRP plays a role in the fetal cardiovascular and metabolic defence to hypoxaemia by affecting sympathetic outflow.

(Received 18 February 2005; accepted after revision 27 April 2005; first published online 28 April 2005)
Corresponding author D. A. Giussani: Department of Physiology, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK.  Email: dag26{at}cam.ac.uk