Losartan and tempol treatments normalize the increased response to hydrogen peroxide in resistance arteries from hypertensive rats.

OBJECTIVE To analyse the role of angiotensin II, via AT1 receptors, and oxidative stress in the mechanisms underlying the increased response to hydrogen peroxide (H2O2) of mesenteric resistance arteries from spontaneously hypertensive rats (SHRs). METHODS Arteries from normotensive and SHRs untreated or treated with the AT1 receptor antagonist, losartan (15 mg/kg per day, 12 weeks), or with the superoxide dismutase analogue, tempol (1 mmol/l, 17 days), were used. Arteries were mounted in microvascular myographs for isometric tension recording; superoxide anion (O2(*-)) production was evaluated by dihydroethidium fluorescence, thromboxane A2 production by enzyme immunoassay and plasma nitrite levels by the Griess method. RESULTS H2O2 (1-100 micromol/l) induced higher contractile responses in mesenteric resistance arteries from hypertensive than normotensive rats. In SHRs, losartan and tempol treatments induced the following effects: normalized the increased H2O2 contractile responses observed; modified neither the inhibitory effects of the cyclooxygenase inhibitor, indomethacin [1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1-H-indole-3-acetic acid] (1 micromol/l), and the thromboxane A2/prostaglandin H2 receptor antagonist, SQ 29 548 (1 micromol/l), on H2O2 contraction, nor the increase in thromboxane A2 production in response to H2O2; abolished the increased vascular O2(*-) production; increased both the potentiatory effect of the nitric oxide inhibitor, N(G)-nitro-L-arginine methyl ester (100 micromol/l), on H2O2 responses and the acetylcholine-induced relaxation. Moreover, losartan treatment abolished the effect of the O2(*-) scavenger, tiron (1 mmol/l), on H2O2 responses and increased plasma nitrite levels. CONCLUSION Nitric oxide removal by an excessive O2(*-) production, probably from an upregulated renin-angiotensin system, participates in the increased response to H2O2 in mesenteric resistance arteries from SHRs.