EFFECT OF L-ARGININE ON RENAL BLOOD-FLOW IN NORMAL SUBJECTS AND PATIENTS WITH HYPOXIC CHRONIC OBSTRUCTIVE PULMONARY-DISEASE

Background - L-arginine is the precursor of endothelium derived nitric oxide (NO) and increasing the available substrate may increase the pr oduction of NO. This has been shown by local infusion in peripheral va scular beds but there are few studies of the effects during systemic i nfusion. Renal vasoconstriction is known to be important in the pathog enesis of cor pulmonale in patients with hypoxic chronic obstructive p ulmonary disease (COPD). The effects of a systemic infusion of L-argin ine on renal and aortic haemodynamics were therefore investigated in n ormal subjects and in patients with hypoxic COPD. Methods - Ten normal volunteers were recruited from the research staff of King's College H ospital. Six patients with COPD and hypoxia (arterial oxygen tension ( PaO2) <8.5 kPa) were recruited from the thoracic medicine outpatient c linic at King's College Hospital and five age and sex matched normal s ubjects were recruited from a group of normal subjects recruited from the database of the Department of Health Care for the Elderly as volun teers for medical research. There was no history of renal, cardiac, or hepatic disease. Baseline values of time averaged mean of the maximum instantaneous velocity (Tamx) and maximum velocity (Vmax) of blood fl ow in intrarenal arteries were obtained using colour flow Doppler ultr asound. Using the same technique, Vmax was obtained ti om the abdomina l aorta just distal to the xiphisternum before and after infusion of L -arginine via a large peripheral vein (20 g in 100 ml sterile water ov er 30 minutes). Results - In normal subjects L-arginine increased bloo d velocity in the intrarenal vessels from a mean of 0.22 m/s to 0.26 m /s, an increase of 19.8%, There was no effect on arterial blood pressu re, heart rate, or aortic blood velocity. L-arginine had no effect on intrarenal or aortic blood velocity in patients with hypoxic COPD. In age matched controls L-arginine increased blood velocity in the intrar enal vessels from a mean of 0.20 m/s to 0.26 m/s, an increase of 36.8% . There was no effect on arterial blood pressure, heart rate, or aorti c blood velocity. Conclusions - L-arginine, at the doses administered, increased renal blood flow, as assessed by renal arterial velocity. T his effect was not seen in patients with hypoxic COPD but was present in age matched controls. This suggests that the abnormal renal vascula r control seen in hypoxic patients with COPD may reflect a disturbance of the L-arginine/nitric oxide pathway.