Effect of nitric oxide inhibition on secretion of atrial
natriuretic factor in isolated rat heart.
Melo, Luis Gabriel, and Harald Sonnenberg.
Department of Physiology, University of Toronto, Toronto, Ontario,
Canada, M5S 1A8
APStracts 2:0337H, 1995.
In addition to stretch, some hormones and neurotransmitters influence
ANF secretion from the mammalian heart. In the present study, we
investigated the effect of specific inhibition of nitric
oxide/endothelium-derived relaxing factor (NO/EDRF) on release of ANF
from the isolated, spontaneously beating heart 1) during basal
conditions and 2) in response to AVP (3 x 10-8 M), Ach (1 x 10-6 M)
and ANG II (4 x 10-7 M), in order to determine if nitric oxide (NO)is
involved as a mediator of basal and hormone-modulated secretion of
ANF. Basal secretion from control hearts remained stable for the
duration of the experiment. Intracoronary perfusion of the heart with
AVP, ACh and ANG II reduced ANF secretion significantly by 58 +/- 4
%, 51 +/- 6% and 26 +/- 8% respectively, independently of concomitant
changes in coronary flow and heart rate. The NO donor sodium
nitroprusside (SNP, 1 x 10-4 M) inhibited ANF secretion comparably to
AVP and Ach. The effect of SNP was not affected by inhibition of
nitric oxide synthase activity with L-NAME (3 x 10-5 M). Similarly,
L-arginine (3 x 10-4 M) but not its stereoisomer D-arginine (3 x 10-4
M) significantly reduced ANF secretion. Subsequent perfusion with AVP
singly or in combination with L-arginine or D-arginine did not affect
ANF secretion further. The inhibitor of nitric oxide synthase NG
-monomethyl-L-arginine (L-NMMA, 3 x 10-5 M) did not affect basal
secretion, but prrevented the inhibitory effect of AVP and Ach. The
effect of ANG II was not changed by L-NMMA. These results indicate
that AVP and Ach inhibit ANF secretion in the isolated heart
indirectly by stimulating NO/EDRF, and suggest a novel function of
NO/EDRF as a negative modulator of ANF secretion.
Received 16 August 1994; accepted in final form 18 July 1995.
APS Manuscript Number H736-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 14 August 1995.