ANGIOTENSIN-II AND CARDIOVASCULAR CHEMOREFLEX RESPONSES TO ACUTE-HYPOXIA IN LATE-GESTATION FETAL SHEEP

1. In six intact and nine carotid sinus denervated (CSD) fetal sheep ( 125-128 days gestation) we measured heart rate (FHR), mean systemic ar terial blood pressure (MAP), femoral and carotid blood flows (FBF and CBF), and femoral and carotid vascular resistances (FVR and CVR). Thre e experiments were conducted on successive days: normoxia followed by acute isocapnic hypoxia (P-a,P-O2 to ca 12 mmHg) with infusion of vehi cle (HV experiment), the same protocol but with infusion of the angiot ensin converting enzyme (ACE) inhibitor, captopril (HC experiment), an d normoxia alone with captopril infusion (NC experiment). Plasma angio tensin 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 N-G-nitro-L-arginine methyl ester (L-NA ME) or saline vehicle. 2. During normoxia, cardiovascular parameters a nd plasma [AIT] were unaltered by captopril infusion, apart from a fal l 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. 3. At the onset of hypoxia the rapid initial fall in FHR and rise in FVR was attenuated in CSD fetus es. In all fetuses FHR returned towards prehypoxic levels as hypoxia c ontinued. In contrast, during hypoxia with vehicle infusion (HV experi ment) plasma [AII] rose to a similar level in intact and CSD fetuses. 4. In both intact and CSD fetuses, the rise in [AII] during hypoxia wa s blocked by captopril or L-NAME infusion. In CSD, but not intact, fet uses infused with captopril the rise in MAP was absent, and the fall i n FBF and rise in PVR did not reach significance during hypoxia. 5. Th us, during normoxia CSD alone, or combined with ACE inhibition, does n ot consistently alter basal cardiovascular control in the late gestati on fetus. The rise in [AIT] during hypoxia is not mediated by carotid reflexes but may involve NO-dependent mechanisms. In intact fetuses, A II does not appear to be pivotal in cardiovascular control during hypo xia. It is only when carotid reflex mechanisms are removed that a role for AII in the regulation of MAP and peripheral blood flow during hyp oxia becomes apparent. These findings lend weight to the idea of multi ple mechanisms of fetal cardiovascular control during hypoxia.