Published Online
on October 23, 2006

A more recent version of this article appeared on December 1, 2006

This Article Full Text (PDF) All Versions of this Article: 48/6/1080    most recent 01.HYP.0000249511.96555.57v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Xu, H. Articles by Galligan, J. J. Search for Related Content PubMed PubMed Citation Articles by Xu, H. Articles by Galligan, J. J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Antioxidants High Blood Pressure Related Collections Animal models of human disease Other hypertension Other Vascular biology

Submitted on August 10, 2006
Revised on August 30, 2006

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

Hui Xu^*; William F. Jackson; Gregory D. Fink; and James J. Galligan

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

^* To whom correspondence should be addressed. E-mail: xuhui2{at}msu.edu.

Abstract--Large-conductance Ca²⁺-activated potassium (BK) channels modulate vascular tone. Tempol, an O^-₂ 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 O^-₂ 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 • O^-₂ • vascular BK channel • myocytes • hypertension

This article has been cited by other articles:

				T. Schluter, U. Zimmermann, C. Protzel, B. Miehe, K.-J. Klebingat, R. Rettig, and O. Grisk Intrarenal artery superoxide is mainly NADPH oxidase-derived and modulates endothelium-dependent dilation in elderly patients Cardiovasc Res, November 12, 2009; (2009) cvp346v2. [Abstract] [Full Text] [PDF]

				N. J. Rusch BK channels in cardiovascular disease: a complex story of channel dysregulation Am J Physiol Heart Circ Physiol, November 1, 2009; 297(5): H1580 - H1582. [Full Text] [PDF]

				L. Pang and N. J. Rusch High-conductance, Ca2+-activated K+ Channels: Altered Expression Profiles in Aging and Cardiovascular Disease Mol. Interv., October 1, 2009; 9(5): 230 - 233. [Full Text] [PDF]

				C. S. Wilcox and A. Pearlman Chemistry and Antihypertensive Effects of Tempol and Other Nitroxides Pharmacol. Rev., December 1, 2008; 60(4): 418 - 469. [Abstract] [Full Text] [PDF]

				M. Li, X. Dai, S. Watts, D. Kreulen, and G. Fink Increased superoxide levels in ganglia and sympathoexcitation are involved in sarafotoxin 6c-induced hypertension Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2008; 295(5): R1546 - R1554. [Abstract] [Full Text] [PDF]

				V. G. DeMarco, J. Habibi, A. T. Whaley-Connell, R. I. Schneider, R. L. Heller, J. P. Bosanquet, M. R. Hayden, K. Delcour, S. A. Cooper, B. T. Andresen, et al. Oxidative stress contributes to pulmonary hypertension in the transgenic (mRen2)27 rat Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2659 - H2668. [Abstract] [Full Text] [PDF]

				A. Just, C. L. Whitten, and W. J. Arendshorst Reactive oxygen species participate in acute renal vasoconstrictor responses induced by ETA and ETB receptors Am J Physiol Renal Physiol, April 1, 2008; 294(4): F719 - F728. [Abstract] [Full Text] [PDF]

				X. Chen, K. Patel, S. G. Connors, M. Mendonca, W. J. Welch, and C. S. Wilcox Acute antihypertensive action of Tempol in the spontaneously hypertensive rat Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3246 - H3253. [Abstract] [Full Text] [PDF]