Angiotensin II and cardiovascular chemoreflex responses to acute hypoxia in late gestation fetal sheep
Corresponding author M. A. Hanson: Department of Obstetrics and Gynaecology, University College London, 86–96 Chenies Mews, London WC1E 6HX, UK. Email: email@example.com
- 1In six intact and nine carotid sinus denervated (CSD) fetal sheep (125–128 days gestation) we measured heart rate (FHR), mean systemic arterial blood pressure (MAP), femoral and carotid blood flows (FBF and CBF), and femoral and carotid vascular resistances (FVR and CVR). Three experiments were conducted on successive days: normoxia followed by acute isocapnic hypoxia (Pa,O2 to ca 12 mmHg) with infusion of vehicle (HV experiment), the same protocol but with infusion of the angiotensin converting enzyme (ACE) inhibitor, captopril (HC experiment), and normoxia alone with captopril infusion (NC experiment). Plasma angiotensin II concentration ([AII]) was measured in these fetuses, and in a separate group of fetuses (n= 5) that were infused with the nitric oxide (NO) synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) or saline vehicle.
- 2During normoxia, cardiovascular parameters and plasma [AII] were unaltered by captopril infusion, apart from a fall in MAP (NC experiment only, P < 0.05) and FHR (HC experiment only, P < 0.05) in intact and CSD fetuses, respectively. No differences were observed between intact and CSD groups.
- 3At the onset of hypoxia the rapid initial fall in FHR and rise in FVR was attenuated in CSD fetuses. In all fetuses FHR returned towards prehypoxic levels as hypoxia continued. In contrast, during hypoxia with vehicle infusion (HV experiment) plasma [AII] rose to a similar level in intact and CSD fetuses.
- 4In both intact and CSD fetuses, the rise in [AII] during hypoxia was blocked by captopril or L-NAME infusion. In CSD, but not intact, fetuses infused with captopril the rise in MAP was absent, and the fall in FBF and rise in FVR did not reach significance during hypoxia.
- 5Thus, during normoxia CSD alone, or combined with ACE inhibition, does not consistently alter basal cardiovascular control in the late gestation fetus. The rise in [AII] during hypoxia is not mediated by carotid reflexes but may involve NO-dependent mechanisms. In intact fetuses, AII does not appear to be pivotal in cardiovascular control during hypoxia. It is only when carotid reflex mechanisms are removed that a role for AII in the regulation of MAP and peripheral blood flow during hypoxia becomes apparent. These findings lend weight to the idea of multiple mechanisms of fetal cardiovascular control during hypoxia.