Effects of oral L-arginine on plasma nitrate and blood pressure in cortisol-treated humans.
OBJECTIVE
The aim of this study was to determine whether cortisol-induced hypertension can be reversed by co-administration of oral L-arginine.


METHODS
Three studies were undertaken in healthy male human subjects. The first study addressed the effect of oral L-arginine loading on plasma arginine concentration. Study 2 addressed the effect of co-administration of cortisol with L-arginine on plasma L-arginine concentrations. Study 3 was a randomized placebo crossover control comparing the effects of cortisol 80 mg/day co-administered with a placebo to cortisol 80 mg/day co-administered with L-arginine 21 g/day.


METHODS
Blood pressure was measured by a random Hawksley sphygmomanometer. Plasma nitrate/nitrite concentrations were measured by a modified Greiss reaction. Plasma arginine and citrulline concentrations were measured by an automated amino acid analyser.


RESULTS
Plasma arginine concentrations were doubled by oral doses of 15 g/day and 21 g/day of L-arginine (study 1). Co-administration of cortisol did not alter plasma arginine concentrations in subjects taking 21 g of L-arginine per day (study 2). Co-administration of L-arginine 21 g/day with cortisol 80 mg/day did not prevent cortisol-induced increases in blood pressure or cortisol-induced falls in plasma nitrate/nitrite concentrations.


CONCLUSIONS
Cortisol-induced hypertension is accompanied by a fall in plasma nitrate/nitrite concentrations. Oral L-arginine administration does not prevent cortisol-induced falls in plasma nitrate/nitrite concentrations or increases in blood pressure. We propose that cortisol-induced reductions in nitrate/nitrite production occur at a point distal to L-arginine availability in the nitric oxide synthase pathway.
Kelly
J J
JJ
Department of Renal Medicine, University of New South Wales, St George Hospital, Sydney, Australia. john.kelly@unsw.edu.au
Williamson
P
P
Martin
A
A
Whitworth
J A
JA
D000284:Administration, Oral; D001120:Arginine / Q000097:blood / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D008297:Male; D009566:Nitrates / Q000097:blood*; D009569:Nitric Oxide / Q000096:biosynthesis*; D010865:Pilot Projects
D009566:Nitrates; D009569:Nitric Oxide; D001120:Arginine; D006854:Hydrocortisone