Pulmonary vascular pressure effects by endothelin-1 in normoxia and
chronic hypoxia, a longitudinal study.
Tjen-A-Looi, S., R. Ekman, J. Osborn, I. Keith.
Department of Comparative Biosciences, School of Veterinary
Medicine, University of Wisconsin-Madison, Department of Psychiatry
and Neurochemistry, University of Gothenburg, Sweden, and Department
of Physiology, University of Minnesota
APStracts 3:0218H, 1996.
The role of Endothelin-1 (ET-1) in pulmonary arterial pressure (Ppa)
homeostasis and hypoxia induced pulmonary hypertension (HPH) was
examined. ET-1 was chronically infused (2 and 4 pmol/kg/min.) into
the pulmonary circulation of male Sprague Dawley rats for 3, 7, and
14 days while in normoxia or hypobaric hypoxia (FiO2 10%). The role
of endogenous ET was examined by infusion of ET-antiserum (ET-AS,
0.25 and 0.5 [mu]l/rat/h, cross-reacting with ET-1, 2 and 3) or the
ETA receptor blocker BQ123 (10 pmol/kg/min.). ET-1 (4 pmol) increased
Ppa at 3 and 7 days in normoxia and hypoxia and was ineffective at 14
days, probably from ETA receptor downregulation. BQ123 blunted the
hypoxic Ppa rise at all times, confirming a role of ETA receptors.
ET-AS (0.5[mu]l) was mostly ineffective but exacerbated hypoxic Ppa
at 14 days contrary to BQ123, suggesting that a different ET receptor
could be involved. ET-1 infusion (2 pmol) caused right ventricular
hypertrophy (RVH) in normoxia and exacerbated RVH in hypoxia, whereas
BQ123 and ET-AS (0.25[mu]l) reduced hypoxic RVH. In conclusion,
endogenous ET-1 plays a role in HPH and RVH by augmenting the level
of hypoxic response. ET-1 also affects HCT and may reduce blood
levels of the vasodilator CGRP.
Received 11 August 1995; accepted in final form 9 May 1996.
APS Manuscript Number H759-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 June 96