Published Online
on October 10, 2005

A more recent version of this article appeared on November 1, 2005

This Article Full Text (PDF) All Versions of this Article: 46/5/1154    most recent 01.HYP.0000186278.50275.fav1 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 Hlavacova, A. Search for Related Content PubMed PubMed Citation Articles by Xu, H. Articles by Hlavacova, A. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Blood Pressure Medicines High Blood Pressure Hazardous Substances DB SODIUM CHLORIDE Related Collections Cardiovascular Pharmacology Animal models of human disease Other hypertension Endothelium/vascular type/nitric oxide

Submitted on July 17, 2005
Revised on July 17, 2005

Activation of Vascular BK Channel by Tempol in DOCA-Salt Hypertensive Rats

Hui Xu^*; Xiaochun Bian; Stephanie W. Watts; and Alexandra Hlavacova

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 smooth muscle tone. Tempol, a superoxide dismutase (SOD) mimetic, lowers blood pressure and inhibits sympathetic nerve activity in normotensive and hypertensive rats. In the present study, we tested the hypotheses depressor responses caused by tempol are partly mediated by vasodilation. It was found that tempol, but not tiron (a superoxide scavenger), dose-dependently relaxed mesenteric arteries (MA) in anesthetized sham and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Tempol also reduced perfusion pressure in isolated, norepinephrine (NE) preconstricted MA from sham and DOCA-salt hypertensive rats. Maximal responses in DOCA-salt rats were twice as large as those in sham rats. The vasodilation caused by tempol was blocked by iberiotoxin (IBTX, BK channel antagonist, 0.1 µmol/L) and tetraethylammonium chloride (TEA) (1 mmol/L). Tempol did not relax KCl preconstricted arteries in sham or DOCA-salt rats, and N-nitro-L-arginine methyl ester (L-NAME), apamin, or glibenclamide did not alter tempol-induced vasodilation. IBTX constricted MA and this response was larger in DOCA-salt compared with sham rats. Western blots and immunohistochemical analysis revealed increased expression of BK channel subunit protein in DOCA-salt arteries compared with sham arteries. Whole-cell patch clamp studies revealed that tempol enhanced BK channel currents in HEK-293 cells transiently transfected with mslo, the murine BK channel a subunit. These currents were blocked by IBTX. The data indicate that tempol activates BK channels and this effect contributes to depressor responses caused by tempol. Upregulation of the BK channel subunit contributes to the enhanced depressor response caused by tempol in DOCA-salt hypertension.

Key words: antioxidants • hypertension • vasodilation

This article has been cited by other articles:

				T. Kathiresan, M. Harvey, S. Orchard, Y. Sakai, and B. Sokolowski A Protein Interaction Network for the Large Conductance Ca2+-activated K+ Channel in the Mouse Cochlea Mol. Cell. Proteomics, August 1, 2009; 8(8): 1972 - 1987. [Abstract] [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]

				A. Lopez-Ruiz, J. Sartori-Valinotti, L. L. Yanes, R. Iliescu, and J. F. Reckelhoff Sex differences in control of blood pressure: role of oxidative stress in hypertension in females Am J Physiol Heart Circ Physiol, August 1, 2008; 295(2): H466 - H474. [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]

				Y. Chen, A. Pearlman, Z. Luo, and C. S. Wilcox Hydrogen peroxide mediates a transient vasorelaxation with tempol during oxidative stress Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2085 - H2092. [Abstract] [Full Text] [PDF]

				A. Just, A. J. M. Olson, C. L. Whitten, and W. J. Arendshorst Superoxide mediates acute renal vasoconstriction produced by angiotensin II and catecholamines by a mechanism independent of nitric oxide Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H83 - H92. [Abstract] [Full Text] [PDF]

				T. Schluter, R. Grimm, A. Steinbach, G. Lorenz, R. Rettig, and O. Grisk Neonatal sympathectomy reduces NADPH oxidase activity and vascular resistance in spontaneously hypertensive rat kidneys Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2006; 291(2): R391 - R399. [Abstract] [Full Text] [PDF]

				K. Thakali, L. Davenport, G. D. Fink, and S. W. Watts Pleiotropic Effects of Hydrogen Peroxide in Arteries and Veins From Normotensive and Hypertensive Rats Hypertension, March 1, 2006; 47(3): 482 - 487. [Abstract] [Full Text] [PDF]