Vascular relaxation response to hydrogen peroxide is impaired in hypertension

Abstract

1. In phenylephrine (1 μM)-precontracted rat superior mesenteric arteries (MA), hydrogen peroxide (H 2O 2, 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 H 2O 2 was smaller in spontaneously hypertensive rats (SHR) when compared with normotensive Wistar-Kyoto rats (WKY). 2. The mechanisms for the attenuated relaxation to H 2O 2 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 H 2O 2 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. H 2O 2 (1 mM) greatly enhanced the frequency and intensity of the spontaneous transient outward K + currents in SHR MA, and the effects of H 2O 2 were inhibited by iberiotoxin, while in WKY MA the K + currents induced by H 2O 2 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 H 2O 2 was smaller in SHR than in WKY, which may account for the attenuated relaxation response to H 2O 2 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 H 2O 2 was found in SHR MA when compared to WKY. In contrast to the activation of K v channels in WKY, H 2O 2 markedly enhanced K Ca activity in SHR, resulting in an attenuation of the increase in mean outward K + current density in response to H 2O 2. These results suggest that alteration in K + channel activation by reactive oxygen species may play a role in the development of hypertension in SHR.