Blocking et a-receptors prevents ischemia and reperfusion injury in
rat lungs.
Khimenko, Pavel L., Timothy M. Moore, and Aubrey E. Taylor.
Department of Physiology, College of Medicine, University of South
Alabama, Mobile, Alabama 36688
APStracts 2:0358A, 1995.
The effects of ETA- and ETB-receptor agonist and antagonists were
studied in isolated buffer perfused rat lungs subjected to 45 minutes
of ischemia followed by 105 minutes of reperfusion (I/R). For the I/R
group after 30 and 90 minutes of reperfusion the Kfc had increased
three and five fold above control, respectively (p<0.01), and
the number of circulating neutrophils in the perfusate decreased by
65+/-7.65%. Both an ETA-receptor antagonist (BQ-610) and an ETAB
-receptor antagonist (PD-156707-0015) given before the ischemic period
protected the lung endothelial barrier from injury associated with
I/R. Also these compounds attenuated the I/R-induced neutrophil
accumulation in the lung (31.94+/-4.16%, and 34.38+/-1.05%,
p<0.01, as compared to I/R, respectively). Neither an ETB
-receptor agonist (IRL-1620) nor an ETB-receptor antagonist (IRL-1038)
affected the I/R-induced endothelial injury. In addition, they did
not alter the number of circulating polymorphonuclear cells during
I/R. ET-1 administration alone, caused a dose-dependent increase in
pulmonary arterial pressure but no measurable increase in
microvascular permeability occurred. We conclude that ET-1 is
involved in I/R-induced lung endothelial injury and speculate that it
acts in concert with some other coactivator(s), most likely PAF,
through ETA-receptors. This mechanism requires polymorphonuclear
leukocytes activation with subsequent release of oxygen radicals
and/or expression of adhesive molecules on the neutrophil surface.
Received 10 April 1995; accepted in final form 7 August 1995.
APS Manuscript Number A388-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 14 August 1995.