QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: mol.104.008953v1 67/5/1723    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tang, G. Articles by Wang, R. Search for Related Content PubMed PubMed Citation Articles by Tang, G. Articles by Wang, R.

ORIGINAL ARTICLE

The Effect of Hydroxylamine on K_ATP Channels in Vascular Smooth Muscle and Underlying Mechanisms

Departments of Physiology (G.T., R.W.) and Pharmacology (L.W.), College of Medicine, University of Saskatchewan, Saskatoon, Canada

Abstract

Hydroxylamine (HA) is a putative intermediate in the conversion of L-arginine to nitric oxide (NO). HA was reported to cause the relaxation of precontracted aorta strips; however, the ionic mechanisms of HA-induced vasorelaxation were not yet known. In the present study, the whole-cell patch-clamp technique was used to examine the effects of HA on ATP-sensitive K⁺ (K_ATP) currents and membrane potentials in vascular smooth muscle cells from rat mesenteric arteries and underlying mechanisms. It was found that bath-applied HA reversibly enhanced K_ATP currents in a concentration-dependent fashion with an EC₅₀ of 54 ± 3.4 µM and hyperpolarized the cell membrane from –48 ± 5.2 to –65 ± 7.5 mV (n = 6, p < 0.01). The increase in K_ATP currents induced by HA was suppressed by superoxide dismutase (–380 ± 45 to –160 ± 20 pA, n = 4, p < 0.01) and N-acetyl-L-cysteine (–385 ± 55 to –150 ± 16 pA, n = 5, p < 0.01), indicating the involvement of different free radicals, including superoxide anion. Hypoxanthine/xanthine oxidase increased not only basal K_ATP currents, but also HA-enhanced K_ATP currents (from –355 ± 40 to –480 ± 62 pA, n = 6, p < 0.05). Sodium nitroprusside, a spontaneous NO donor, and a membrane-permeable cGMP analog (8-bromo-cGMP) were without effects on HA-enhanced K_ATP currents or basal K_ATP currents. Our results indicate that HA augmented K_ATP channel activity and hyperpolarized cell membrane, possibly via increased free radical generation.

Address correspondence to: Dr. Rui Wang, FAHA, Department of Physiology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK S7N 5E5, Canada. E-mail: rui.wang{at}lakeheadu.ca

This article has been cited by other articles:

				J. Jiao, V. Garg, B. Yang, T. S. Elton, and K. Hu Protein Kinase C-{epsilon} Induces Caveolin-Dependent Internalization of Vascular Adenosine 5'-Triphosphate-Sensitive K+ Channels Hypertension, September 1, 2008; 52(3): 499 - 506. [Abstract] [Full Text] [PDF]

				K. R. Olson, L. G. Forgan, R. A. Dombkowski, and M. E. Forster Oxygen dependency of hydrogen sulfide-mediated vasoconstriction in cyclostome aortas J. Exp. Biol., July 15, 2008; 211(14): 2205 - 2213. [Abstract] [Full Text] [PDF]