Mechanism of anoxia-induced atrial natriuretic peptide release in
the isolated rat atria.
Skvorak, John P., E. Truitt Sutton, Papineni S. Rao, and John R.
Dietz.
Departments of Physiology and Biophysics and Obstetrics and
Gynecology, University of South Florida, College of Medicine, Tampa,
FL 33612
APStracts 3:0064R, 1996.
Our laboratory has recently shown that locally produced endothelin
(ET) is involved in the atrial natriuretic peptide (ANP) response to
a physical stimulus, stretch. The aim of this study was to determine
if factors locally produced in the atria were involved in the ANP
response to a chemical stimulus, anoxia. Reduced oxygen tension is a
potent stimulus of ANP release and our results show that when
isolated perfused atria were exposed to anoxic conditions, the ANP
secretion rate increased by a maximum of 129 +/- 8% of the baseline.
Exposure to anoxia neither caused an of elevation in perfusate
creatinine phosphokinase, a change in atrial morphology detectable by
electron microscopy, nor interfered with the return toward the
baseline ANP secretion rate with reoxygenation suggesting that this
response was not due to myocyte damage. When the atria were
pretreated with either 3 [mu]M BQ-123, an endothelin receptor
inhibitor, or 10 [mu]M indomethacin, a cyclooxygenase inhibitor, the
ANP response to anoxia was nearly abolished. To clarify the
association between ET and prostaglandins, we showed that the ANP
response to 50 nM ET-1 was totally blocked at both high and low
pressure by 10 [mu]M indomethacin but the increased contractility
response to ET was unaffected. Therefore, we have concluded that the
anoxia-induced ANP response is mediated by locally produced ET which,
in turn, stimulates the production of prostaglandins. Prostaglandins
appear to be responsible for the increased ANP secretion rate.
Received 6 November 1995; accepted in final form 15 February 1996
APS Manuscript Number R690-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 March 96