Lung mechanics and pulmonary but not systemic vascular responses to
i.v. endothelin-1 in sheep are thromboxane and infusion rate
-dependent.
Faltin, Daniel L., Andreas Weber, J. Sylvain Lacroix, Manuel Jorge
-Costa, and Denis R. Morel.
Division of Anesthesiological Investigations, Department of
Anesthesia, Pharmacology and Surgical Intensive Care, and Clinic of
ENT Surgery, University Hospital of Geneva, CH-1211 Geneva 14 -
Switzerland
APStracts 2:0558A, 1995.
The role of cyclooxygenase metabolites formation in the systemic and
pulmonary vascular and airway response to different i.v. infusion
rates of endothelin-1 (ET-1 was investigated in eight barbiturate
-anesthetized, mechanically ventilated adult sheep. ET-1 (20, 200 and
400 pmol/kg) was infused into the femoral vein either over 1, 10, or
180 s before and after pretreatment with indomethacin (1.5 mg/kg
i.v.). ET-1 infusion produced a dose-dependent systemic
vasoconstriction that was similar with all three infusion rates. In
contrast, the pulmonary vascular and airways responses to ET-1 were
not only dose-dependent, but also infusion rate-dependent, so that
consistent effects on the pulmonary vasculature and airways were
observed only when the peptide was injected over 1 s. At the highest
dosage and at the fastest rate of administration, ET-1 produced a
five-fold rise in pulmonary vascular resistance, a two-fold rise in
airway resistance, and a 45% decrease in dynamic pulmonary
compliance, whereas no changes were observed when the peptide was
injected over 180 s. Plasma levels of 6-k-PGF1 increased 20-fold when
ET-1 was administered over 1 s, but only five-fold when administered
over 180 s. TxB2 increased 5-fold when ET-1 was administered over 1 s
and did not increase when ET-1 was given over 180 s. Plasma TxB2
levels were linearly correlated with pulmonary vascular or airway
resistance during the bolus ET-1 infusion. Pretreatment with
indomethacin completely prevented the ET-1-induced rise in TxB2 and
6-k-PGF1 and blocked pulmonary vaso- and broncho-constriction
observed, whereas it enhanced systemic vasoconstriction. These
results demonstrate that in adult sheep, i.v. ET-1 produces pulmonary
vaso- and bronchoconstriction that is infusion rate-dependent and is
associated with the rate-dependent production of thromboxane. In
contrast, the increase in systemic vascular tone elicited by ET-1 is
not affected by its rate of infusion and does not depend on the
secondary generation of cyclooxygenase metabolites.
Received 7 February 1995; accepted in final form 8 December 1995.
APS Manuscript Number A142-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 December 95