Vascular relaxation response to hydrogen peroxide is impaired in hypertension
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abstract
In phenylephrine (1 μM)‐precontracted rat superior mesenteric arteries (MA), hydrogen peroxide (H2O2, 0.3 and 1 mM) caused a biphasic response: a transient contraction followed by a relaxation. In the presence of thromboxane A2/prostaglandin H2 (TP) receptor antagonist (SQ 29548), the contractile component of the biphasic response was abolished. The relaxation response to H2O2 was smaller in spontaneously hypertensive rats (SHR) when compared with normotensive Wistar–Kyoto rats (WKY).The mechanisms for the attenuated relaxation to H2O2 in the SHR were studied. KCl (40 mM) prevented the relaxation response. Calcium‐dependent K+ channel (KCa) blockers (tetraethylammonium chloride, TEA; iberiotoxin, and charybdotoxin) showed a greater inhibition of H2O2 relaxation in SHR than in WKY, whereas voltage‐dependent K+‐channel (Kv) blocker 4‐aminopyridine was more effective in inhibiting the relaxation in WKY than in SHR.H2O2 (1 mM) greatly enhanced the frequency and intensity of the spontaneous transient outward K+ currents in SHR MA, and the effects of H2O2 were inhibited by iberiotoxin, while in WKY MA the K+ currents induced by H2O2 were mainly of the Kv type. The consequence of the activation of different types of K+ channel was that the net increase in mean outward K+ current density in response to H2O2 was smaller in SHR than in WKY, which may account for the attenuated relaxation response to H2O2 in the SHR.The contractile responses of MA to TEA, iberiotoxin, and charybdotoxin were greater in SHR than in WKY.In summary, an attenuated relaxation response to H2O2 was found in SHR MA when compared to WKY. In contrast to the activation of Kv channels in WKY, H2O2 markedly enhanced KCa activity in SHR, resulting in an attenuation of the increase in mean outward K+ current density in response to H2O2. These results suggest that alteration in K+ channel activation by reactive oxygen species may play a role in the development of hypertension in SHR.British Journal of Pharmacology (2004) 142, 143–149. doi:10.1038/sj.bjp.0705727
