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

1 The present study analyses the influence of hypertension and endothelium on the effect induced by hydrogen peroxide (H 2 O 2 ) 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 m m ) or cumulative (100 n m –10 m m ) concentrations of H 2 O 2 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 H 2 O 2 scavenger) abolished the contraction elicited by 1 m m H 2 O 2 in both strains. 3 Superoxide dismutase (SOD, 150 u ml −1 ) and dimethylsulphoxide (DMSO, 7 m m ), scavengers of superoxide anions and hydroxyl radicals, respectively, did not alter H 2 O 2 ‐induced contractions in intact segments from both strains. However, l ‐N G ‐nitroarginine methyl ester ( l ‐NAME, 100 μ m , a nitric oxide synthase inhibitor) increased the response to H 2 O 2 in normotensive rats, although the increase was less than that produced by endothelium removal. 4 Incubation of segments with 1 m m H 2 O 2 for 15 min and subsequent washout reduced the contractile responses induced by 75 m m 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 μ m , a cyclo‐oxygenase inhibitor) and SQ 29,548 (10 μ m , a prostaglandin H 2 /thromboxane A 2 receptor antagonist) practically abolished the contractions elicited by H 2 O 2 in normotensive and hypertensive rats. 6 We conclude that: (1) the oxidant stress induced by H 2 O 2 produces contractions mediated by generation of a product of the cyclo‐oxygenase pathway, prostaglandin H 2 or more probably thromboxane A 2 , in normotensive and hypertensive rats; (2) oxygen‐derived free radicals are not involved in the effect of H 2 O 2 ; (3) in normotensive rats, endothelium protects against H 2 O 2 ‐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 H 2 O 2 , that is lost in hypertension.British Journal of Pharmacology (1998) 125 , 1329–1335; doi: 10.1038/sj.bjp.0702200