AJP - Heart and Circulatory Physiology, Vol 271, Issue 6 2447-H2453, Copyright © 1996 by American Physiological Society
Superoxide and nitroglycerin stimulate release of PGF2 alpha and TxA2 in isolated rat heart
S. A. Gupte, T. Okada and R. Ochi
Department of Physiology, Juntendo University School of Medicine, Tokyo, Japan.
The aim of this study was to investigate the effects of nitroglycerin
(NTG), a nitric oxide (NO) donor used as a vasodilating agent, on
prostanoid [e.g., prostaglandin (PG)] release in the O2(-)-pretreated rat
heart. Perfusion of O2-, 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 during the control period to 72.2 +/- 3.9
mmHg, P < 0.05). O2- caused increased release of PGF2 alpha from 3.6 +/-
0.7 to 20.6 +/- 4.4 pmol.min-1.g-1 and of thromboxane A2 (TxA2) from 2.4
+/- 0.4 to 9.6 +/- 1.6 pmol.min-1.g-1 (P < 0.001) with no significant
changes in PGE2 and PGI2 release. During the 20-min washout of O2- from the
heart with normal Krebs solution, release of PGF2 alpha and TxA2 decreased
to 8.7 +/- 1.4 and 6.3 +/- 1.7 pmol.min-1.g-1, respectively, and the
release of PGE2 and PGI2 markedly increased from 11.1 +/- 2.9 to 25.4 +/-
3.6 and 157.2 +/- 16.4 to 413.2 +/- 41.4 pmol.min-1.g-1, respectively (P
< 0.05), without lowering the elevated CPP. Administration of 4 microM
NTG during the washout period paradoxically augmented the elevated CPP to
133.3 +/- 0.6% and was associated with a doubling (P < 0.05) of PGF2
alpha and TxA2 release with no significant changes in PGE2 and PGI2
release. The NTG-induced CPP elevation was inhibited (P < 0.05) by
indomethacin, a cyclooxygenase inhibitor, or ONO-3708, a TxA2 receptor
blocker, whereas arachidonic acid, a substrate for PG synthesis, augmented
the CPP elevation. These results indicate that NTG stimulates the synthesis
of vasoconstrictive PG in the O2(-)-pretreated rat heart, inducing a
paradoxical elevation in CPP.
