Endothelin acts as a paracrine regulator of stretch induced atrial
natriuretic peptide release.
Skvorak, John P., Stanley J. Nazian, and John R. Dietz.
Department of Physiology and Biophysics, University of South
Florida, College of Medicine, Tampa, FL 33612
APStracts 2:0152R, 1995.
Several lines of evidence suggest a paracrine regulatory role for
endothelin (ET) in the release of ANP. To investigate this
possibility, we used the ET A-type receptor (ETA-R) competitive
inhibitor cyclo(D-Asp-Pro-D-Val-Leu-D-Trp) (BQ-123) in isolated
perfused atria to determine the effect of endogenously produced ET on
the release of ANP. Initially, we found that at high pressure (8-10
mmHg) increased the mean ANP secretion rate by 117.3 +/- 21.2% (p
< .05). Next, we found that at high pressure, 50 nM of
exogenously applied ET significantly augmented the stretch induced
release of ANP (p < .05) and that this response could be
significantly attenuated, in a dose dependent manner, by 1 and 3
[mu]M BQ-123 (p < .05). These experiments proved the efficacy of
the inhibitor in our model. Subsequently, we found that the stretch
induced release of ANP was significantly reduced to 51.5 +/- 13.0%
and 22.3 +/- 11.8% by 1 and 3 [mu]M BQ-123, respectively (p <
.05). Since the perfused atria model eliminates systemic
cardiovascular effects, allows control and direct recording of the
intra-atrial pressure, and preserves the potential endothelium
-myocyte control system, we conclude that the stretch induced release
of ANP is partially regulated by ET and that the ET is locally
produced and constitutes a paracrine control system.
Received 24 February 1995; accepted in final form 31 May 1995.
APS Manuscript Number R135-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 June 1995.