In order to determine the relative contributions of endothelial-derived nitric oxide (NO) versus intravascular nitrogen oxide species in the regulation of human blood flow, we simultaneously measured forearm blood flow and arterial and venous levels of plasma nitrite, low and high molecular weight S-nitrosothiols, and red cell S-nitrosohemoglobin (SNO-Hb). Measurements were made at rest and during regional inhibition of NO synthesis with L-NMMA (30% decrease in flow). Surprisingly, we found significant circulating arterial-venous plasma nitrite gradients (540 +/- 74 nM and 466 +/- 79 nM respectively; p<0.05 for A-V gradient), that were unchanged during L-NMMA infusion. However, during subsequent exercise, the consumption of nitrite increased from 156 +/- 59 to 1583 +/- 517 pmol/ml/min/100 gm tissue (p<0.05). The role of circulating S-nitrosothiols and SNO-Hb in the regulation of basal vascular tone is less certain. We found that low molecular weight S-nitrosothiols were undetectable and S-nitroso(SNO)-albumin levels were two logs lower than previously reported (arterial levels of 44.9 +/- 14 nM). In fact SNO-albumin primarily formed in the venous circulation (63.4 +/- 13 nM), even during NO synthase inhibition. While SNO-Hb was measurable in the human circulation (brachial artery levels of 170 nM in whole blood), arterial-venous gradients were not significant and delivery of NO from SNO-Hb was minimal, even during L-NMMA infusion and exercise. We conclude that 1) circulating nitrite is bioactive and provides a delivery gradient of intravascular NO, 2) SNO-albumin does not deliver NO from the lungs to the tissue but forms in the peripheral circulation, and 3) SNO-Hb and S-nitrosothiols play a minimal role in the regulation of basal vascular tone, even during exercise stress.
| Schechter, Alan N; Gladwin, Mark T; Cannon 3rd, Richard O (2002) NO solutions? J Clin Invest 109:1149-51 |
| Thompson, K L; Rosenzweig, B A; Honchel, R et al. (2001) Loss of critical palindromic transgene promoter sequence in chemically induced Tg.AC mouse skin papillomas expressing transgene-derived mRNA. Mol Carcinog 32:176-86 |
| Gladwin, M T; Shelhamer, J H; Schechter, A N et al. (2000) Role of circulating nitrite and S-nitrosohemoglobin in the regulation of regional blood flow in humans. Proc Natl Acad Sci U S A 97:11482-7 |
