July 15, 2001Journal of Clinical Investigation262 citationsOpen Access
Effects of inhaled nitric oxide on regional blood flow are consistent with intravascular nitric oxidedelivery
Key Result
Inhaled nitric oxide blocked the 25% reduction in blood flow and 50% increase in vascular resistance caused by regional NO synthesis inhibition with L-NMMA, maintaining normal vascular function.
Structured PICO
Does inhaled nitric oxide improve regional blood flow in healthy volunteers during regional blockade of NO synthesis?
P
Population
16 healthy adult volunteers (50% female, mean age 33 years) without risk factors for endothelial dysfunction underwent forearm blood flow measurements.
I
Intervention
Inhaled nitric oxide (NO) at 80 parts per million (ppm) for 1 hour via face mask, during intra-arterial infusion of L-NMMA (8 µmol/min) and forearm exercise.
C
Comparator
Room air breathing during intra-arterial infusion of L-NMMA and forearm exercise.
O
Outcome
Forearm blood flow and forearm vascular resistance.surrogate
Inhaled nitric oxide can supply intravascular NO to maintain normal vascular function during regional blockade of NO synthesis, suggesting potential therapeutic applications for conditions characterized by endothelial dysfunction.
Limitations
- The effects of NO breathing on vasculature constricted by other agonists with regional NO synthesis intact was not determined, so it is uncertain if the vascular effects are specific to deficient regional NO synthesis.
- Potential instability of high-molecular-weight S-nitrosothiols in plasma may have limited their detection during NO breathing.
Abstract
Nitric oxide (NO) may be stabilized by binding to hemoglobin, by nitrosating thiol-containing plasma molecules, or by conversion to nitrite, all reactions potentially preserving its bioactivity in blood. Here we examined the contribution of blood-transported NO to regional vascular tone in humans before and during NO inhalation. While breathing room air and then room air with NO at 80 parts per million, forearm blood flow was measured in 16 subjects at rest and after blockade of forearm NO synthesis with N(G)-monomethyl-L-arginine (L-NMMA) followed by forearm exercise stress. L-NMMA reduced blood flow by 25% and increased resistance by 50%, an effect that was blocked by NO inhalation. With NO inhalation, resistance was significantly lower during L-NMMA infusion, both at rest and during repetitive hand-grip exercise. S-nitrosohemoglobin and plasma S-nitrosothiols did not change with NO inhalation. Arterial nitrite levels increased by 11% and arterial nitrosyl(heme)hemoglobin levels increased tenfold to the micromolar range, and both measures were consistently higher in the arterial than in venous blood. S-nitrosohemoglobin levels were in the nanomolar range, with no significant artery-to-vein gradients. These results indicate that inhaled NO during blockade of regional NO synthesis can supply intravascular NO to maintain normal vascular function. This effect may have application for the treatment of diseases characterized by endothelial dysfunction.