cyclic-gmp and Intermittent-Claudication

Administration of L-arginine improves nitric oxide (NO) formation and endothelium-dependent vasodilation in atherosclerotic patients.. We investigated in this double-blind, controlled study whether prolonged intermittent infusion therapy with L-arginine improves the clinical symptoms of patients with intermittent claudication, as compared with the endothelium-independent vasodilator prostaglandin E1, and control patients.. Thirty-nine patients with intermittent claudication were randomly assigned to receive 2 x 8 g L-arginine/day, or 2 x 40 microg prostaglandin E1 (PGE1)/day or no hemodynamically active treatment, for 3 weeks. The pain-free and absolute walking distances were assessed on a walking treadmill at 3 km/h, 12% slope, and NO-mediated, flow-induced vasodilation of the femoral artery was assessed by ultrasonography at baseline, at 1, 2 and 3 weeks of therapy and 6 weeks after the end of treatment. Urinary nitrate and cyclic guanosine-3', 5'-monophosphate (GMP) were assessed as indices of endogenous NO production.. L-Arginine improved the pain-free walking distance by 230+/-63% and the absolute walking distance by 155+/-48% (each p < 0.05). Prostaglandin E1 improved both parameters by 209+/-63% and 144+/-28%, respectively (each p < 0.05), whereas control patients experienced no significant change. L-Arginine therapy also improved endothelium-dependent vasodilation in the femoral artery, whereas PGE1 had no such effect. There was a significant linear correlation between the L-arginine/asymmetric dimethylarginine (ADMA) ratio and the pain-free walking distance at baseline (r=0.359, p < 0.03). L-Arginine treatment elevated the plasma L-arginine/ADMA ratio and increased urinary nitrate and cyclic GMP excretion rates, indicating normalized endogenous NO formation. Prostaglandin E1 therapy had no significant effect on any of these parameters. Symptom scores assessed on a visual analog scale increased from 3.51+/-0.18 to 83+/-0.4 (L-arginine) and 7.0+/-0.5 (PGE1; each p < 0.05), but did not significantly change in the control group (4.3+/-0.4).. Restoring NO formation and endothelium-dependent vasodilation by L-arginine improves the clinical symptoms of intermittent claudication in patients with peripheral arterial occlusive disease.

Topics: Aged; Aged, 80 and over; Alprostadil; Arginine; Arterial Occlusive Diseases; Blood Flow Velocity; Chronic Disease; Cyclic GMP; Double-Blind Method; Exercise Test; Female; Femoral Artery; Follow-Up Studies; Humans; Infusions, Intravenous; Intermittent Claudication; Leg; Male; Middle Aged; Nitrates; Nitric Oxide; Peripheral Vascular Diseases; Treatment Outcome; Ultrasonography, Doppler, Duplex; Vasodilation; Vasodilator Agents

Local activation of polymorphonuclear leukocytes (PMNLs) is considered an important aspect of the pathogenesis of intermittent claudication, although concrete mechanisms of their effects on circulatory homeostasis in peripheral atherosclerotic disease remain unclear. This study evaluated the ability of PMNLs to deactivate nitric oxide (NO), a key regulator of regional circulation, as a possible factor determining PMNL involvement into ischemic disorders in patients who have intermittent claudication before and after vascular reconstruction.. A total of 57 patients who had peripheral occlusive disease in an aortofemoral segment before surgical treatment (group 1) and 65 patients who had similar occlusive lesions and other clinical and demographic data 6 to 12 months after undergoing inflow vascular reconstruction (group 2) were examined. All patients from group 2 had anatomically patent grafts; their satisfaction and level of function after surgical treatment were assessed by a five-point questionnaire. The sex- and age-matched control group included 35 subjects. NO activity was bioassayed by measuring its ability to increase cyclic guanosine monophosphate (cGMP) accumulation in rat fetal lung-cultured fibroblasts (RFL-6 cells). The ability of PMNLs to deactivate NO was characterized as the percent decrease in NO-induced cGMP accumulation in RFL-6 cells.. Stimulated PMNLs caused inhibition of the activity of authentic NO; accumulation of cGMP induced by sodium nitroprusside was not affected. PMNLs from patients with peripheral atherosclerotic disease either before or after vascular reconstruction had a more marked capacity of NO inactivating than the cells from healthy subjects. For both groups of patients, levels of PMNL-induced NO deactivation were higher for patients with diabetes, and especially both diabetes and arterial hypertension. For both groups of patients, there was no correlation between levels of PMNL-induced NO deactivation and resting ankle-brachial indexes (ABIs). In contrast, close correlation was revealed between levels of PMNL-induced NO deactivation and postexercise ABIs and percent decrease in resting ABIs after exercise in patients evaluated either before or after surgical treatment.. The ability of stimulated PMNLs to deactivate NO is elevated in peripheral occlusive disease and may be implicated in the pathogenesis of intermittent claudication. In patients who underwent successful recanalization of magistral arteries, levels of PMNL-induced NO deactivation remained higher than in control subjects. The increase in the ability of PMNL to deactivate NO positively correlated to ABI decreases after exercise in patients with peripheral occlusive disease either before or after surgical treatment.

Topics: Animals; Aortic Diseases; Arteriosclerosis; Blood Circulation; Blood Pressure; Case-Control Studies; Cells, Cultured; Cyclic GMP; Diabetes Mellitus; Female; Femoral Artery; Fibroblasts; Homeostasis; Humans; Hypertension; Intermittent Claudication; Ischemia; Lung; Male; Middle Aged; Neutrophil Activation; Neutrophils; Nitric Oxide; Nitroprusside; Patient Satisfaction; Peripheral Vascular Diseases; Rats; Vascular Patency