Superoxide and nitroglycerin stimulates the release of
prostaglandin f 2 and thromboxane a 2 in the isolated rat heart.
Gupte, Sachin A., Takao Okada, and Rikuo Ochi.
Department of Physiology, Juntendo University School of Medicine,
Tokyo, Japan
APStracts 3:0257H, 1996.
The aim of this study was to investigate the effects of nitroglycerin
(NTG), a nitric oxide (NO)-donor used as a vasodilating agent, on
prostanoids (PG) release in the O 2 - -pretreated rat heart.
Perfusion of O 2 -, generated by a xanthine oxidase-purine coupling,
caused elevation (p<0.05) of the coronary perfusion pressure
(CPP) after 20 min (from 57.1+/-3.9 mmHg during the control period to
72.2+/-3.9 mmHg, p<0.05). O 2 - caused increased release of PGF
2 [alpha] from 3.6+/-0.7 to 20.6+/-4.4 pmol/min/g and of TXA 2 from
2.4+/-0.4 to 9.6+/-1.6 pmol/min/g (p<0.001) with no significant
changes in PGE 2 and PGI 2 release. During the wash out (20 min) of O
2 - from the heart with normal Krebs solution, release of PGF 2
[alpha] and TXA 2 decreased to 8.7+/-1.4 and 6.3+/-1.7 pmol/min/g
respectively, and release of PGE 2 and PGI 2 markedly increased from
11.1+/-2.9 to 25.4+/-3.6 and 157.2+/-16.4 to 413.2+/-41.4 pmol/min/g,
respectively (p<0.05) without lowering the elevated CPP.
Administration of 4 [mu]M NTG during the wash out period
paradoxically augmented the elevated CPP to 133.3+/-0.6% and was
associated with a doubling (p<0.05) of PGF 2 [alpha] and TXA 2
release, with no significant changes in PGE 2 and PGI 2 release. The
NTG-induced CPP elevation was inhibited (p<0.05) by
indomethacin, a cyclooxygenase inhibitor or ONO-3708, a TXA 2
receptor blocker, while arachidonic acid, a substrate for PG
synthesis augmented the CPP elevation. These results indicate that
NTG stimulates the synthesis of vasoconstrictive PGs in the O 2 -
-pretreated rat heart inducing a paradoxical elevation in CPP.
Received 15 April 1996; accepted in final form 3 June 1996.
APS Manuscript Number H328-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 4 July 96