L-NMMA significantly inhibited reactive hyperemia in normal controls (P=0.0011) but not in patients with atherosclerosis or risk factors, demonstrating abnormal nitric oxide bioactivity.
Case-Control (n=44)
Does nitric oxide contribute to reactive hyperemia, and does L-arginine improve reactive hyperemia in patients with atherosclerosis or endothelial dysfunction?
Nitric oxide contributes to reactive hyperemia in the normal human peripheral vasculature, but this NO bioactivity is diminished in patients with atherosclerosis and is not improved by acute L-arginine administration.
p-value: p=0.0011
Our objectives were to (1) test the hypothesis that nitric oxide (NO) contributes to peak reactive hyperemia (RH) in the human peripheral vasculature, (2) examine the impact of atherosclerosis and its risk factors on RH, and (3) investigate whether L-arginine will improve RH in patients with endothelial dysfunction. The endothelium contributes to shear stress-mediated vasomotion by releasing a variety of dilating factors, including NO, but the contribution of NO to peak RH in patients with and without endothelial dysfunction is unknown. Endothelium-dependent and endothelium-independent function was assessed with intrafemoral arterial acetylcholine (ACh) and sodium nitroprusside. RH was produced by occlusion of blood flow to the leg for 3 minutes. The study was repeated after NG-monomethyl-L-arginine (L-NMMA) in 44 subjects and L-arginine in 9 patients with atherosclerosis. There were 15 normal control subjects without risk factors for atherosclerosis and 29 patients with risk factors or angiographic atherosclerosis. Microvascular vasodilation in response to ACh, but not to sodium nitroprusside, was lower in the patients with risk factors or atherosclerosis compared with normal control subjects, P=0.048, and the inhibition of ACh-induced microvascular dilation by L-NMMA was also greater in normal control subjects (P=0.045). Similarly, RH, including the peak response, was inhibited by L-NMMA in normal control subjects (P=0.0011) but not in patients with risk factors or atherosclerosis, suggesting that the contribution of NO to both ACh-induced dilation and RH was diminished in patients with risk factors or atherosclerosis. L-Arginine did not affect vasodilation in response to ACh, sodium nitroprusside, or RH. We concluded that (1) NO contributes to all phases of RH in the normal human peripheral vasculature, (2) patients with atherosclerosis or its risks have abnormal NO bioactivity in response to pharmacological and physiological stimulation, and (3) L-arginine does not improve RH in atherosclerosis. Reduced physiological vasodilation in atherosclerosis may contribute to or exacerbate hypertension and ischemia.
Dakak et al. (1998) conducted a case-control in Atherosclerosis and endothelial dysfunction (n=44). L-NMMA and L-arginine vs. Normal controls vs patients with atherosclerosis was evaluated on Inhibition of reactive hyperemia by L-NMMA (p=0.0011). L-NMMA significantly inhibited reactive hyperemia in normal controls (P=0.0011) but not in patients with atherosclerosis or risk factors, demonstrating abnormal nitric oxide bioactivity.