Contractile responses elicited by hydrogen peroxide in aorta from normotensive and hypertensive rats. Endothelial modulation and mechanism involved

Abstract

1. The present study analyses the influence of hypertension and endothelium on the effect induced by hydrogen peroxide (H₂O₂) on basal tone in aortic segments from normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) of 6-month-old, as well as the possible mechanisms involved.

2. Single (1 mM) or cumulative (100 nM–10 mM) concentrations of H₂O₂ produced a transient contraction or a concentration-dependent increase of basal tone, respectively, in segments from WKY and SHR. In both cases, the contractions were higher in intact segments from hypertensive than from normotensive rats, and increased by endothelium removal in both strains. Catalase (1000 u ml⁻¹, a H₂O₂ scavenger) abolished the contraction elicited by 1 mM H₂O₂ in both strains.

3. Superoxide dismutase (SOD, 150 u ml⁻¹) and dimethylsulphoxide (DMSO, 7 mM), scavengers of superoxide anions and hydroxyl radicals, respectively, did not alter H₂O₂-induced contractions in intact segments from both strains. However, L-N^G-nitroarginine methyl ester (L-NAME, 100 μM, a nitric oxide synthase inhibitor) increased the response to H₂O₂ in normotensive rats, although the increase was less than that produced by endothelium removal.

4. Incubation of segments with 1 mM H₂O₂ for 15 min and subsequent washout reduced the contractile responses induced by 75 mM KCl in intact segments from SHR and in endothelium-denuded segments from both strains; this effect being prevented by catalase (1000 u ml⁻¹).

5. Indomethacin (10 μM, a cyclo-oxygenase inhibitor) and SQ 29,548 (10 μM, a prostaglandin H₂/thromboxane A₂ receptor antagonist) practically abolished the contractions elicited by H₂O₂ in normotensive and hypertensive rats.

6. We conclude that: (1) the oxidant stress induced by H₂O₂ produces contractions mediated by generation of a product of the cyclo-oxygenase pathway, prostaglandin H₂ or more probably thromboxane A₂, in normotensive and hypertensive rats; (2) oxygen-derived free radicals are not involved in the effect of H₂O₂; (3) in normotensive rats, endothelium protects against H₂O₂-mediated injury to contractile machinery, determined by the impairment of KCl-induced contractions; and (4) endothelial nitric oxide has a protective role on the contractile effect induced by H₂O₂, that is lost in hypertension.

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