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(Hypertension. 2006;48:1080.)
© 2006 American Heart Association, Inc.

Original Articles

Activation of Potassium Channels by Tempol in Arterial Smooth Muscle Cells From Normotensive and Deoxycorticosterone Acetate-Salt Hypertensive Rats

From the Department of Pharmacology and Toxicology, Michigan State University, East Lansing.

Correspondence to Hui Xu, Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824. E-mail xuhui2{at}msu.edu

Large-conductance Ca²⁺-activated potassium (BK) channels modulate vascular tone. Tempol, an O₂^– dismutase mimetic, causes vasodilation via activation of vascular BK channels. In this study, we investigated the mechanisms underlying tempol-induced activation of BK channels in mesenteric arterial (MA) myocytes from sham and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. In sham myocytes, whole-cell patch clamp studies showed that tempol enhanced peak outward currents (I_o). This effect was larger in DOCA-salt myocytes. Tempol caused a leftward shift in the activation curve for I_o in sham and DOCA-salt myocytes. In DOCA-salt myocytes, the peak I_o at +80 mV did not differ from sham myocytes, but iberiotoxin (BK channel blocker) caused a larger reduction of I_o in DOCA-salt compared with sham myocytes. Iberiotoxin but not 4-aminopyridine blocked the I_o activated by tempol. Tiron, another O₂^– scavenger, had no effect on I_o. Using inside-out patches, we found that tempol caused a 4-fold increase in open probability (P_o) of BK channels but did not change the mean channel open time in sham and DOCA-salt myocytes. Tempol did not change single channel conductance in sham or DOCA-salt myocytes. Western blot and immunocytochemical studies revealed that BK channel -subunit expression was increased in DOCA-salt MA compared with sham MA. The data indicate that tempol directly activates BK channels by increasing channel P_o. We conclude that upregulation of the BK channel -subunit protein and tempol-induced increases in BK channel P_o contribute to the enhanced depressor response caused by tempol in DOCA-salt hypertensive rats.

Key Words: tempol • O₂^–vascular BK channel • myocytes • hypertension

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