RT Journal Article SR Electronic T1 The Effect of Hydroxylamine on KATP Channels in Vascular Smooth Muscle and Underlying Mechanisms JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 1723 OP 1731 DO 10.1124/mol.104.008953 VO 67 IS 5 A1 Guanghua Tang A1 Lingyun Wu A1 Rui Wang YR 2005 UL http://molpharm.aspetjournals.org/content/67/5/1723.abstract AB 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 < 0.01). The increase in KATP 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 KATP currents, but also HA-enhanced KATP 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 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.