Effect of L-arginine on renal blood flow in normal subjects and patients with hypoxic chronic obstructive pulmonary disease.

Abstract

Background -L-arginine is the precursor of endothelium derived nitric oxide (NO) and increasing the available substrate may increase the production of NO. This has been shown by local infusion in peripheral vascular beds but there are few studies of the effects during systemic infusion. Renal vasoconstriction is known to be important in the pathogenesis of cor pulmonale in patients with hypoxic chronic obstructive pulmonary disease (COPD). The effects of a systemic infusion of L-arginine on renal and aortic haemodynamics were therefore investigated in normal subjects and in patients with hypoxic COPD. Methods -Ten normal volunteers were recruited from the research staff of King's College Hospital. Six patients with COPD and hypoxia (arterial oxygen tension (Pao2) <8 5 kPa) were recruited from the thoracic medicine outpatient clinic at King's College Hospital and five age and sex matched normal subjects were recruited from a group of normal subjects recruited from the database of the Department of Health Care for the Elderly as volunteers for medical research. There was no history ofrenal, cardiac, or hepatic disease. Baseline values of time averaged mean of the maximum instantaneous velocity (Tamx) and maximum velocity (Vmax) ofblood flow in intrarenal arteries were obtained using colour flow Doppler ultrasound. Using the same technique, Vmax was obtained from the abdominal 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 over 30 minutes). Results -In normal subjects L-arginine increased blood velocity in the intrarenal vessels from a mean of0*22 mis to 0*26 mis, an increase of 19-8%. There was no effect on arterial blood pressure, 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 intrarenal vessels from a mean of 0 20 m/s to 0 26 mis, an increase of 36-8%. There was no effect on arterial blood pressure, heart rate, or aortic blood velocity. Conclusions -L-arginine, at the doses administered, increased renal blood flow, as assessed by renal arterial velocity. This effect was not seen in patients with hypoxic COPD but was present in age matched controls. This suggests that the abnormal renal vascular control seen in hypoxic patients with COPD may reflect a disturbance of the L-arginine/nitric oxide pathway.

Chronic hypoxia increases MCA contractile response to U-46619 by reducing NO production and/or activity

“…Supporting a possible limitation by L-arginine, L-arginine supplementation raised NO production (8) and decreased hypoxic pulmonary vasoconstriction and pulmonary vascular remodeling in chronically hypoxic rats (21). Effects of L-arginine supplementation are not limited to the pulmonary circulation, as shown by increased renal blood flow after systemic L-arginine infusion (13). Chronic hypoxia has been shown to impair L-arginine uptake (8), suggesting that this may be one mechanism by which chronic hypoxia might limit NO production.…”

“…Administration of the nonspecific NO synthase (NOS) inhibitor nitro-L-arginine (NLA) eliminated the difference in contractile sensitivity between the vessels from the normoxic and chronically hypoxic animals, suggesting that reduction in NO production and/or activity was responsible for the increased contractile sensitivity observed. Because cofactors for NOS are not saturating in the cerebral circulation (25) and dietary supplementation with L-arginine has been shown to at least partially reverse hypoxia-associated increases in contractile responsiveness in other circulations (13,21), we reasoned that dietary supplementation with L-arginine might restore NO production and/or activity and thereby reduce contractile sensitivity in vessels from chronically hypoxic animals to normoxic values. Results indicated that this did not occur, suggesting that other factors served to reduce NO production and augment MCA contractility under conditions of chronic hypoxia.…”

Expression of Adhesion Molecules and G Proteins in Circulating Neutrophils in Chronic Obstructive Pulmonary Disease

“…There is evidence in the literature to support both possibilities. On the one hand, endothelial function appears to be abnormal in smokers (24,25) and in patients with COPD (26,27). On the other, the number of peripheral capillaries appears to be reduced in COPD (28).…”

Fluid homeostasis in chronic obstructive lung disease

“…When hypercapnia complicates COPD, the vasodilatory responses to dopamine [30], L-arginine [33], protein loading [34] and even oxygen [30] are lost. Whether this means that structural changes make the renal vasculature less responsive, is not known.…”