Journal of Applied Physiology, Vol 70, Issue 3 1228-1234, Copyright © 1991 by American Physiological Society

ARTICLES

Tone-dependent responses to endothelin in the isolated perfused fetal sheep pulmonary circulation in situ

S. Cassin, V. Kristova, T. Davis, P. Kadowitz and G. Gause
Department of Physiology, College of Medicine, University of Florida, Gainesville 32610.

Pulmonary vascular responses to endothelin (ET-1), a peptide derived from endothelial cells in culture, were investigated in the ovine fetus delivered by cesarean section from chloralose-anesthetized ewes with intact umbilical circulation. Circulation to the lower left lobe of the fetal lung was isolated in situ and perfused at constant flow with blood withdrawn from the inferior vena cava. Injection of graded doses of ET-1 into the left pulmonary artery decreased pulmonary arterial perfusion pressure in a dose-related manner. At doses of 100, 300, and 1,000 ng, pulmonary vascular resistance per kilogram body weight (PVR/kg) was decreased 30, 40, and 42%, respectively. However, when fetuses were ventilated with 100% oxygen, 100- and 300-ng doses of ET-1 decreased PVR/kg by 5 and 9%, respectively. In contrast, injection of 1,000 ng of ET-1 resulted in a reversal of the response, and PVR/kg was increased by 70%. Ventilation of the right lung alone resulted in a similar reversal of the vasodilator response to 1,000 ng of ET-1, and a 138% increase in PVR/kg was recorded. These studies demonstrate for the first time that ET-1 has vasodilator activity in the normally high-tone ovine fetal pulmonary circulation. In addition, these results show that ET-1 has vasoconstrictor activity in the newly ventilated low-tone pulmonary vasculature. The present data indicate the pulmonary vascular responses to ET-1 are tone dependent in the ovine fetal pulmonary circulation.

This article has been cited by other articles:

				N. Skovgaard, H. Zibrandtsen, B. E. Laursen, U. Simonsen, and T. Wang Hypoxia-induced vasoconstriction in alligator (Alligator mississippiensis) intrapulmonary arteries: a role for endothelin-1? J. Exp. Biol., May 15, 2008; 211(10): 1565 - 1570. [Abstract] [Full Text] [PDF]

				S. M. Black, E. Mata-Greenwood, R. W. Dettman, B. Ovadia, R. K. Fitzgerald, O. Reinhartz, S. Thelitz, R. H. Steinhorn, R. Gerrets, K. Hendricks-Munoz, et al. Emergence of Smooth Muscle Cell Endothelin B-Mediated Vasoconstriction in Lambs With Experimental Congenital Heart Disease and Increased Pulmonary Blood Flow Circulation, September 30, 2003; 108(13): 1646 - 1654. [Abstract] [Full Text] [PDF]

				S. Bonnet, A. Belus, J.-M. Hyvelin, E. Roux, R. Marthan, and J.-P. Savineau Effect of chronic hypoxia on agonist-induced tone and calcium signaling in rat pulmonary artery Am J Physiol Lung Cell Mol Physiol, July 1, 2001; 281(1): L193 - L201. [Abstract] [Full Text] [PDF]

				D. Dunbar Ivy, T. A. Parker, and S. H. Abman Prolonged endothelin B receptor blockade causes pulmonary hypertension in the ovine fetus Am J Physiol Lung Cell Mol Physiol, October 1, 2000; 279(4): L758 - L765. [Abstract] [Full Text] [PDF]

				D. Dunbar Ivy, T. D. le Cras, T. A. Parker, J. P. Zenge, M. Jakkula, N. E. Markham, J. P. Kinsella, and S. H. Abman Developmental changes in endothelin expression and activity in the ovine fetal lung Am J Physiol Lung Cell Mol Physiol, April 1, 2000; 278(4): L785 - L793. [Abstract] [Full Text] [PDF]

				D. Dunbar Ivy, T. D. Le Cras, M. P. Horan, and S. H. Abman Increased lung preproET-1 and decreased ETB-receptor gene expression in fetal pulmonary hypertension Am J Physiol Lung Cell Mol Physiol, April 1, 1998; 274(4): L535 - L541. [Abstract] [Full Text] [PDF]

				S. A. Barman Pulmonary vasoreactivity to serotonin during hypoxia is modulated by ATP-sensitive potassium channels J Appl Physiol, August 1, 1997; 83(2): 569 - 574. [Abstract] [Full Text] [PDF]

				M. Okada, C. Yamashita, M. Okada, and K. Okada Role of Endothelin-1 in Beagles With Dehydromonocrotaline-Induced Pulmonary Hypertension Circulation, July 1, 1995; 92(1): 114 - 119. [Abstract] [Full Text]