S. Tsuchida et al., ATTENUATION OF SODIUM-NITROPRUSSIDE RESPONSES AFTER PROLONGED INCUBATION OF RAT AORTA WITH ENDOTOXIN, American journal of physiology. Heart and circulatory physiology, 36(6), 1994, pp. 80002305-80002310
We investigated the effects of prolonged treatment with Escherichia co
li lipopolysaccharide (LPS) on the responses to sodium nitroprusside (
SNP) in endothelium-denuded rat aortic strips. Incubation of the aorti
c strips with LPS for 24 h dramatically attenuated relaxation and guan
osine 3',5'-cyclic monophosphate (cGMP) formation by SNP, which were s
ignificantly restored by the inhibition of nitric oxide (NO) productio
n with Nw-nitro-L-arginine, In the aorta coincubated with LPS and prot
ein synthesis inhibitor (dexamethasone or cycloheximide, which prevent
s induction of endotoxin-inducible NO synthase), no attenuation of the
relaxation was observed and the cGMP formation was significantly rest
ored. Relaxation response to 8-bromo-cGMP or papaverine was not attenu
ated, even after 24 h of incubation. These results suggest that the at
tenuation of SNP responses is mainly associated with a decrease in the
activation of guanylate cyclase (GC) as a consequence of the prolonge
d exposure to muscle-derived NO. Moreover SNP in the presence of methy
lene blue evoked a small but apparent relaxation of 24-h-incubated aor
ta without significant elevation of cGMP, suggesting the involvement o
f cGMP-independent pathways in the remaining relaxation produced by SN
P.