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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.

Received for publication November 5, 2004.

Accepted for publication February 16, 2005.

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

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