AJP - Regulatory, Integrative and Comparative Physiology, Vol 266, Issue 3 929-R955, Copyright © 1994 by American Physiological Society

ARTICLES

Systemic and pulmonary hemodynamic effects of big endothelin-1 and phosphoramidon in the ovine fetus

O. W. Jones 3rd and S. H. Abman
Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Denver 80262.

To investigate the potential role of endothelin-1 (ET-1) in fetal vasoregulation, we examined in sheep the hemodynamic effects of infusion of big ET-1 (bET-1; precursor of ET-1) on the systemic and pulmonary circulations in chronically catheterized late-gestation fetuses. Thirteen animals [134 +/- 0.5 (SE) days gestation] received systemic infusions of bET-1 (1.5 or 3.0 micrograms/min for 10 min via the superior vena cava), which increased systemic arterial pressure by 5.0 +/- 1.9 (P < 0.01) and 13.9 +/- 1.8 mmHg (P < 0.01), respectively. Pretreatment with 10 mg of phosphoramidon, an ET-1-converting enzyme inhibitor, blocked the hypertensive response to bET-1. Six animals (136 +/- 1.5 days gestation) received intrapulmonary infusion of bET-1 (3.0 micrograms/min for 10 min via the left pulmonary artery), which increased pulmonary arterial pressure by 18.1 +/- 1.5 mmHg (P < 0.01). Three animals (130 +/- 1.5 days gestation) received phosphoramidon (1 mg/min for 10 min via the left pulmonary artery), which had no observed effect on baseline pulmonary vascular tone. We conclude that bET-1 produces systemic and pulmonary hypertension in the late-gestation fetus. Phosphoramidon inhibits bET-1-induced hypertension, suggesting that the fetus possesses ET-1-converting enzyme activity.

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