TY - JOUR T1 - The Effect of Hydroxylamine on K<sub>ATP</sub> Channels in Vascular Smooth Muscle and Underlying Mechanisms JF - Molecular Pharmacology JO - Mol Pharmacol SP - 1723 LP - 1731 DO - 10.1124/mol.104.008953 VL - 67 IS - 5 AU - Guanghua Tang AU - Lingyun Wu AU - Rui Wang Y1 - 2005/05/01 UR - http://molpharm.aspetjournals.org/content/67/5/1723.abstract N2 - 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+ (KATP) 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 KATP 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 &lt; 0.01). The increase in KATP currents induced by HA was suppressed by superoxide dismutase (–380 ± 45 to –160 ± 20 pA, n = 4, p &lt; 0.01) and N-acetyl-l-cysteine (–385 ± 55 to –150 ± 16 pA, n = 5, p &lt; 0.01), indicating the involvement of different free radicals, including superoxide anion. Hypoxanthine/xanthine oxidase increased not only basal KATP currents, but also HA-enhanced KATP currents (from –355 ± 40 to –480 ± 62 pA, n = 6, p &lt; 0.05). Sodium nitroprusside, a spontaneous NO donor, and a membrane-permeable cGMP analog (8-bromo-cGMP) were without effects on HA-enhanced KATP currents or basal KATP currents. Our results indicate that HA augmented KATP channel activity and hyperpolarized cell membrane, possibly via increased free radical generation. ER -