In-vivo Evidence of Acetylcholine
Stimulated Arginine Transport in Man Parnell MM*, Chin-Dusting
JPF, Starr, J, Kaye DM Alfred Baker Medical Unit, Baker Medical Research
Institute, Prahran, Victoria. L-Arginine
is the precursor for nitric oxide synthesis in the endothelium, which
ultimately leads to endothelium-dependent vasodilation. This study investigated
factors which may regulate endothelial arginine transport, by using endothelium
dependent (Acetylcholine (ACh) and Isoprenaline (ISO)) and independent drugs
(Sodium Nitroprusside (SNP)). We aimed to determine the effects of blood flow
on L-arginine transport of endothelial cells in man. Eight
healthy males (22 ± 1 years; mean ± SEM) with normal mean arterial blood
pressure (87 ± 2 mmHg) were recruited into the study. 6µCi/hr of 3H-L-Arginine
was infused into the brachial artery throughout the course of the study.
Subsequent two minute infusions (2ml/min) of ACh (9.25 and 37 µg/min), ISO (50
and 200 µg/min) and SNP (2 and 8
µg/min) were performed, with a minimum five minute rest period between
each infusion. Forearm blood flow was measured before and after two minutes of
infusion, determined using forearm venous occlusion plethysmography, and blood
samples were obtained following each drug infusion for the determination of
3H-L-Arginine uptake. Arginine uptake was determined by multiplying forearm
plasma flow by arterial 3H-L-Arginine concentration and the extraction ratio. Data
using the endothelium independent vasodilator demonstrates that arginine uptake
(basal 51681 ± 8341 vs. low 26756.67 ± 7544 vs. high dose 27546 ± 6800 of SNP;
p<0.035) is inversely related to plasma flow (basal 16.63 ± 3.37 to low
57.32 ±7.20 to high dose 80.93 ± 9.46 ml/min of SNP; p<0.001). This
study also compared the effects of three different vasodilators on arginine
uptake in the forearm. Similar plasma flows resulting from each drug were
selected for arginine uptake comparison. Under the same blood flow conditions
(ACh 43.79 ± 8.07, ISO 51.55 ± 6.39, SNP 54.86 ± 7.01 ml/min; p=ns) (n=6), SNP
and ISO significantly reduced uptake (basal 51681 ± 8341, ISO 20042 ± 2506, SNP
24572 ± 3368 dpm/min; p<0.01), however no reduction was observed with ACh
(45601 ± 5589 dpm/min; p=ns). These data suggest that arginine uptake is
dependent upon blood flow and furthermore, that ACh stimulates arginine
transport into the endothelium.
