Contribution of Nitric Oxide to Reactive Hyperemia

Abstract

Abstract-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 N G -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, Pϭ0.048, and the inhibition of ACh-induced microvascular dilation by L-NMMA was also greater in normal control subjects (Pϭ0.045). Similarly, RH, including the peak response, was inhibited by L-NMMA in normal control subjects (Pϭ0.0011) 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. (Hypertension. 1998;32:9-15.) Key Words: hyperemia Ⅲ nitric oxide Ⅲ endothelium Ⅲ atherosclerosis M yogenic, neural, and local factors such as adenosine, prostaglandins, and ischemic metabolites are believed to play a critical role in the RH response that is stimulated by transient interruption of blood flow.1-11 The vascular endothelium, by releasing endothelium-derived relaxing factors [12][13][14] or by stimulation of ATP-sensitive potassium channels, also contributes to vascular smooth muscle relaxation, 10,15,16 but the role of these mediators in determining RH in humans remains controversial. The most important endotheliumderived relaxing factor, which plays a pivotal role in modulating smooth muscle tone in the human conductance and resistance vessels, is NO. 12,17,18 Endothelial NO release can be stimulated by physiological changes, including hypoxia and increases in shear stress, both...

Characteristic Features of in vivo Skin Microvascular Reactivity in CADASIL

“…hyperemia is also altered in hypertension, with reduction of both peak and AUC, there is no change of the kinetic parameters of the response (Dakak et al, 1998). Thus, although hypertension is a major risk factor for small artery diseases, the corresponding patterns of the skin microvascular reactivity are distinct from CADASIL.…”

Physiological hyperinsulinaemia increases intramuscular microvascular reactive hyperaemia and vasomotion in healthy volunteers

“…In humans, moreover, insulin has been shown to stimulate vasodilatory effects by inducing endothelial nitric oxide (NO) production [21]. The idea that NO plays a part in intramuscular reactive hyperaemia is supported by most [22,23,24], but not all studies [25] using venous occlusion plethysmography. Therefore, in the present study, enhanced endothelial NO production might have contributed to insulin-mediated changes in intramuscular reactive hyperaemia.…”

Endothelial dysfunction, angiotensin-converting enzyme inhibitors and calcium antagonists

“…5,6 Estimates of endothelial function by this test are remarkably stable over time, but no clear set of normal values has been developed. 7 Because of the different genetic background and variability in the distribution of CVD risk factors, normal values of FMD may differ among populations.…”

“…8,10 An important body of evidence suggests that endothelial dysfunction is a generalised process that is not necessarily confined to vessels with overt atherosclerotic alterations. [4][5][6][7][8][9][10] This proposal is strengthened by the high correlation (Ͼ0.75) reported between the coronary vasomotor response and the peripheral endothelial function of the brachial artery evaluated by FMD. 11,12 Recently, three different groups 10,13,14 have demonstrated that the diagnostic of endothelial dysfunction realised in coronary and peripheral arteries in patients with different stages of coronary artery disease is related with an increased incidence of an adverse long-term outcome of coronary heart disease.…”