The fetal defence to hypoxaemia involves metabolic and cardiovascular responses. These include hyperglycaemia and redistribution of the cardiac output towards the brain and away from peripheral circulations, such as the femoral vascular bed (Giussani et al. 1994). The glycaemic response is mediated by sympathetic pathways and increased catecholamines (Jones et al. 1980). Fetal peripheral vasoconstriction is triggered by a chemoreflex via the sympathetic chain, maintained by catecholamines, and offset by enhanced NO activity (Morrison et al. 2003). The role of calcitonin gene related peptide (CGRP) in fetal cardiovascular and metabolic physiology is unknown, but is gaining interest as it can act both as an autonomic neurotransmitter and as a vasodilator. This study determined the role of CGRP in the glycaemic and peripheral haemodynamic responses to acute hypoxaemia in the ovine fetus during late gestation.

Under halothane anaesthesia, 5 sheep fetuses were prepared with catheters and a Transonic probe around a femoral artery at 0.8 gestation (term ≈ 145 days). Five days later, animals underwent a 2.5 h protocol: 1 h normoxia, 0.5 h hypoxaemia and 1 h recovery, during either saline infusion or treatment with the CGRP antagonist (CGRP_8-37, 50 µg kg^-1 I.A. bolus + 20 µg min^-1 I.V. infusion). Hypoxaemia during saline or antagonist treatment occurred on separate days in randomised order. Treatment started 30 min before hypoxaemia and ran until the end of the challenge. Arterial samples were collected to determine blood gas and metabolic status. At the end of the experiment, animals were humanely killed with pentobarbitone (200 mg kg^-1 I.V.).

Fetal treatment with the CGRP antagonist did not alter basal blood gases, metabolic status or cardiovascular variables. During hypoxaemia, similar falls in P_aO₂ occurred in fetuses during either saline (20.2 ± 0.9 to 10.6 ± 0.7) or antagonist (20.2 ± 0.9 to 10.4 ± 1.1 mmHg) treatment, without alterations in P_aCO₂. Hypoxaemia induced hyperglycaemia, hypertension, bradycardia and femoral vasoconstriction in all fetuses. However, the increments in blood glucose (0.8 ± 0.2 vs. 0.3 ± 0.1 mM) and femoral vascular resistance (Figure) during hypoxaemia were significantly smaller during treatment with the CGRP antagonist (P < 0.05).

These data suggest a role for CGRP in the sympathetic activation of the glycaemic and peripheral vasoconstrictor responses to acute hypoxaemia in the late gestation ovine fetus.

This work was supported by The Journal of Experimental Pathology and The Lister Institute for Preventive Medicine.