Vascular and hormonal responses to arginine: provision of substrate for nitric oxide or non-specific effect?
1. The vascular and hormonal effects of L- and D-arginine were compared in healthy subjects and in patients with insulin-dependent diabetes mellitus or untreated essential hypertension. 2. Infusion of L- or D-arginine (40 mumol/l) in the forearm vascular bed, sufficient to increase the local concentration approximately 20-fold, had no effect on blood flow or the vasodilator response to acetylcholine (30 and 100 nmol/min) in patients with insulin-dependent diabetes (n = 7) or essential hypertension (n = 7), or in age- and sex-matched control subjects (n = 7 in both groups). 3. Systemic infusion of 10 g of L-arginine (n = 5) or D-arginine (n = 3) increased plasma concentration of arginine approximately 20-fold without altering supine or erect haemodynamics. Increases in plasma insulin, prolactin and glucagon were seen with both enantiomers. The stereopurity of arginine was confirmed in a cell-culture assay system. 4. We conclude that, in healthy subjects and patients with essential hypertension or insulin-dependent diabetes, synthesis of nitric oxide within the vasculature is not limited by substrate availability. At high concentrations of arginine, non-stereospecific effects, including alterations in hormone concentration, occur. It remains to be determined whether these non-stereospecific hormonal changes might contribute to certain haemodynamic effects of arginine.
MacAllister
R J
RJ
Department of Pharmacology and Clinical Pharmacology, St George's Hospital Medical School, London, U.K.
Calver
A L
AL
Collier
J
J
Edwards
C M
CM
Herreros
B
B
Nussey
S S
SS
Vallance
P
P
D000328:Adult; D001120:Arginine / Q000097:blood / Q000494:pharmacology*; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D004311:Double-Blind Method; D005260:Female; D005542:Forearm / Q000098:blood supply; D006439:Hemodynamics / Q000187:drug effects*; D006728:Hormones / Q000097:blood; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis*; D011187:Posture / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects
D006728:Hormones; D009569:Nitric Oxide; D001120:Arginine