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+ (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.
- Received November 5, 2004.
- Accepted February 16, 2005.
- The American Society for Pharmacology and Experimental Therapeutics
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