Br J Pharmacol. 1996 May;118(1):57-62.  

Inhibition of NO-medicate responses by 7-ethoxyresorufin, a substrate and
competitive inhibitor of cytochrome P450.

Li CG, Rand MJ.

Department of Medical Laboratory Science, Royal Melbourne Institute of
Technology, Victoria, Australia.

1. The effects of 7-ethoxyresorufin (7-ER), which is a substrate for and
competitive inhibitor of cytochrome P450, were studied on responses to nitric
oxide (NO), the NO donors sodium nitroprusside (SNP) and glyceryl trinitrate
(GTN), acetylcholine-induced endothelium-dependent relaxations of rat and rabbit
aortic rings and nitrergic nerve stimulation-induced relaxations of rat
anococcygeus muscles. 2. In rat and rabbit aortic rings, 7-ER (2 microM)
inhibited the relaxations to acetylcholine in endothelium-intact preparations
and the relaxant action of NO in endothelium-denuded preparations. Relaxant
responses to SNP and GTN were inhibited by 7-ER in the rat but not rabbit aortic
rings. However, the relaxant actions of papaverine and 8-bromo-cyclic GMP were
not affected by 7-ER. 3. In rat anococcygeus muscles, 7ER (2 microM) inhibited
the relaxant action of NO, but relaxations elicited by nitrergic nerve
stimulation were only partly inhibited by a higher concentration of 7-ER (10
microM). 4. After inhibition by 7-ER, superoxide dismutase (100 u ml-1) restored
NO-induced relaxations of the rat aortic rings, but not acetylcholine-, SNP or
GTN-induced relaxations, and restored NO- and nitrergic nerve
stimulation-induced relaxations of anococcygeus muscles. 5. Another cytochrome
P450 inhibitor, troleandomycin (10-30 microM), had no effect on NO- or
acetylcholine-induced relaxations of rat aortic rings and NO- or nitrergic nerve
stimulation-induced relaxations of anococcygeus muscles. However, resorufin, an
analogue of 7-ER, inhibited responses to acetylcholine, NO and GTN in rat aortic
rings. 6. The results suggest that 7-ER inhibited responses to NO and nitrergic
nerve stimulation through generation of superoxide radicals. However, an
additional mechanism may be involved in the reduction in acetylcholine-induced
response in aortic rings. 7. A 7-ER sensitive P450 system may be involved in the
bioactivation of GTN and SNP in rat aortic rings, but not in rabbit aorta or rat
anococcygeus muscles.

PMID: 8733576 [PubMed - indexed for MEDLINE]