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NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

Vasodilator tone in the llama fetus: the role of nitric oxide during normoxemia and hypoxemia

¹Laboratorio de Fisiología y Fisiopatología del Desarrollo, Programa de Fisiopatología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile; ²Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile; ³Department of Physiology, University of Cambridge, and The Lister Institute for Prevention Medicine, Cambridge, United Kingdom; ⁴Department of Paediatrics, University of Maastricht, The Netherlands; ⁵Centre for Fetal Origins of Adult Disease, University of Southampton, Southampton, United Kingdom; and ⁶Centro Internacional de Estudios Andinos, Universidad de Chile, Santiago, Chile

Submitted 2 February 2005 ; accepted in final form 15 May 2005

The fetal llama responds to hypoxemia, with a marked peripheral vasoconstriction but, unlike the sheep, with little or no increase in cerebral blood flow. We tested the hypothesis that the role of nitric oxide (NO) may be increased during hypoxemia in this species, to counterbalance a strong vasoconstrictor effect. Ten fetal llamas were operated under general anesthesia. Mean arterial pressure (MAP), heart rate, cardiac output, total vascular resistance, blood flows, and vascular resistances in cerebral, carotid and femoral vascular beds were determined. Two groups were studied, one with nitric oxide synthase (NOS) blocker N^G-nitro-L-arginine methyl ester (L-NAME), and the other with 0.9% NaCl (control group), during normoxemia, hypoxemia, and recovery. During normoxemia, L-NAME produced an increase in fetal MAP and a rapid bradycardia. Cerebral, carotid, and femoral vascular resistance increased and blood flow decreased to carotid and femoral beds, while cerebral blood flow did not change significantly. However, during hypoxemia cerebral and carotid vascular resistance fell by 44% from its value in normoxemia after L-NAME, although femoral vascular resistance progressively increased and remained high during recovery. We conclude that in the llama fetus: 1) NO has an important role in maintaining a vasodilator tone during both normoxemia and hypoxemia in cerebral and femoral vascular beds and 2) during hypoxemia, NOS blockade unmasked the action of other vasodilator agents that contribute, with nitric oxide, to preserving blood flow and oxygen delivery to the tissues.

N^G-nitro-L-arginine methyl ester; arterial pressure; blood flow; vascular resistance; hypoxia

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