Journal
BRITISH JOURNAL OF PHARMACOLOGY
Volume 142, Issue 1, Pages 143-149Publisher
WILEY
DOI: 10.1038/sj.bjp.0705727
Keywords
hydrogen peroxide; mesenteric artery; potassium channels; reactive oxygen species; relaxation; spontaneously hypertensive rats
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1 In phenylephrine (1 muM)-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 A(2)/prostaglandin H-2 (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). 2 The mechanisms for the attenuated relaxation to H2O2 in the SHR were studied. KCl (40 mM) prevented the relaxation response. Calcium-dependent K+ channel (K-Ca) blockers (tetraethylammonium chloride, TEA; iberiotoxin, and charybdotoxin) showed a greater inhibition of H2O2 relaxation in SHR than in WKY, whereas voltage-dependent K+-channel (K-v) blocker 4-aminopyridine was more effective in inhibiting the relaxation in WKY than in SHR. 3 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 K-v 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. 4 The contractile responses of MA to TEA, iberiotoxin, and charybdotoxin were greater in SHR than in WKY. 5 In summary, an attenuated relaxation response to H2O2 was found in SHR MA when compared to WKY. In contrast to the activation of K-v channels in WKY, H2O2 markedly enhanced K-Ca 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.
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