Aa. Steiner et Lgs. Branco, Carbon monoxide is the heme oxygenase product with a pyretic action: evidence for a cGMP signaling pathway, AM J P-REG, 280(2), 2001, pp. R448-R457
Citations number
46
Categorie Soggetti
Physiology
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
We have recently reported that the central heme oxygenase (HO) pathway has
an important role in the genesis of lipopolysaccharide fever. However, the
HO product involved, i.e., biliverdine, free iron, or carbon monoxide (CO),
has not yet been identified with certainty. Therefore, in the present stud
y, we tested the thermoregulatory effects of all HO products. Body core tem
perature (T-c) and gross activity of awake, freely moving rats was measured
by biotelemetry. Intracerebroventricular administration of heme-lysinate (
152 nmol), which induces the HO pathway, evoked a marked increase in T-c, a
response that was attenuated by intracerebroventricular pretreatment with
the HO inhibitor zinc deuteroporphyrin 2,4-bis glycol (200 nmol), indicatin
g that an HO product has a pyretic action in the central nervous system (CN
S) of rats. Besides, heme-lysinate also increased gross activity, but no co
rrelation was found between this effect and the increase in Tc. Moreover, i
ntracerebroventricular biliverdine or iron salts at 152 nmol, a dose at whi
ch heme-lysinate was effective in increasing T-c, produced no change in T-c
. Accordingly, intracerebroventricular treatment with the iron chelator def
eroxamine elicited no change in basal T-c and did not affect heme-induced p
yresis. However, heme-induced pyresis was completely prevented by the solub
le guanylate cyclase (sGC) inhibitor 1H-[1,2,4] oxadiazolo[ 4,3,-a] quinoxa
line-1-one. Because biliverdine and iron had no thermoregulatory effects an
d CO produces most of its actions via sGC, these data strongly imply that C
O is the only HO product with a pyretic action in the CNS.