Vascular relaxation response to hydrogen peroxide is impaired in hypertension.
1. In phenylephrine (1 microm)-precontracted rat superior mesenteric arteries (MA), hydrogen peroxide (H(2)O(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(2)O(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(2)O(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(2)O(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(2)O(2) (1 mm) greatly enhanced the frequency and intensity of the spontaneous transient outward K(+) currents in SHR MA, and the effects of H(2)O(2) were inhibited by iberiotoxin, while in WKY MA the K(+) currents induced by H(2)O(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(2)O(2) was smaller in SHR than in WKY, which may account for the attenuated relaxation response to H(2)O(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(2)O(2) was found in SHR MA when compared to WKY. In contrast to the activation of K(v) channels in WKY, H(2)O(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(2)O(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.
Gao
Yu-Jing
YJ
Smooth Muscle Research Program, Department of Anaesthesia, McMaster University, Hamilton, Ontario, Canada.
Zhang
Yongde
Y
Hirota
Simon
S
Janssen
Luke J
LJ
Lee
Robert M K W
RM
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D006861:Hydrogen Peroxide