Involvement of nitric oxide in the endothelium‐dependent relaxation induced by hydrogen peroxide in the rabbit aorta

Abstract

1 The effects of hydrogen peroxide (H202, 0.1-1 mM) on the tone of the rings of rabbit aorta precontracted with phenylephrine (0.2-0.3 gAM) were studied.2 H202 induced a concentration-dependent relaxation of both the intact and endothelium-denuded rings. However, in the presence of intact endothelium, H202-induced responses were 2-3 fold larger than in its absence, demonstrating the existence of endothelium-independent and endothelium-dependent components of the vasorelaxant action of H202. 3 The endothelium-dependent component of H202-induced relaxation was prevented by N0-nitro-Larginine methyl ester (L-NAME, 30 gM) or N0-monomethyl-L-arginine (300 JAM), inhibitors of nitric oxide synthase (NOS), in a manner that was reversible by L-, but not by D-arginine (2 mM). The inhibitors of NOS did not affect the responses of denuded rings.4 Methylene blue (10 JAM), an inhibitor of soluble guanylate cyclase, blocked H202-induced relaxation of both the intact and denuded rings. 5 H202 (1 mM) enhanced the efflux of cyclic GMP from both the endothelium-intact and denuded rings. The effect of H202 was 4 fold greater in the presence of intact endothelium and this endotheliumdependent component was abolished after the inhibition of NOS by L-NAME (30 JAM). 6 In contrast to the effects of H202, the vasorelaxant action of stable organic peroxides, tert-butyl hydroperoxide or cumene hydroperoxide, did not have an endothelium-dependent component. Moreover, they did not potentiate the efflux of cyclic GMP from the rings of rabbit aorta. 7 Exogenous donors of NO, specifically, 3-morpholinosydnonimine (SIN-1), glyceryl trinitrate or sodium nitroprusside were used to decrease the tone of denuded rings to the level induced by endogenous NO released from intact endothelium. This procedure did not influence the vasorelaxant activity of H202, showing that H202 does not potentiate the vasorelaxant action of NO within the smooth muscle. 8 Thus, H202-induced relaxation in the rabbit aorta has both endothelium-dependent and independent components. The endothelium-dependent component of the relaxant action of H202 is due to enhanced endothelial synthesis of NO.

Hydrogen Peroxide Activates Endothelial Nitric-oxide Synthase through Coordinated Phosphorylation and Dephosphorylation via a Phosphoinositide 3-Kinase-dependent Signaling Pathway

“…In the current study, we examined the short term implications of H 2 O 2 on eNOS activity in PAECs. We found that H 2 O 2 promotes NO bioactivity measured as the conversion of L-[ (38). The current study extends these findings by elucidating the mechanisms whereby H 2 O 2 can promote activation of eNOS.…”

The inhibitory effect of 3‐amino‐1,2,4‐triazole on relaxation induced by hydroxylamine and sodium azide but not hydrogen peroxide or glyceryl trinitrate in rat aorta

“…We found that low concentrations (100 nM-1 mM) selectively produced relaxation in endothelium-containing rings and this was abolished by L-NAME and methylene blue, inhibitors of nitric oxide synthase and soluble guanylate cyclase, respectively. This component of relaxation thus appeared to result from enhanced production of nitric oxide, as had previously been suggested (Furchgott, 1991;Zembowicz et al, 1993;Furchgott et al, 1994). Higher concentrations of hydrogen peroxide (30 4uM -1 mM), however, produced relaxation of endothelium-denuded rings and this too was inhibited by methylene blue suggesting involvement of soluble guanylate cyclase.…”

Changes in superoxide dismutase mRNA expression by streptozotocin‐induced diabetes

“…Indeed, it has been found that the activity of SOD in various tissues is decreased in the diabetic state (Crouch et al, 1978;Loven et al, 1982; Matkovics et al, 1982;Cohen, 1995). On the other hand, it has been shown that hydrogen peroxide accelerates NO release (Rubanyi & Vanhoutte, 1986b), activates soluble guanylate cyclase activity, and causes smooth muscle relaxation (Zembowicz et al, 1993). Thus, an increase in SOD-induced relaxation in the diabetic state may be due to the overproduction of hydrogen peroxide which may cause smooth muscle relaxation, because diabetes causes a greater production of superoxide anion presumably due to reduced superoxide dismutase activity.…”