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 coadministration of oral L-arginine. Study design: 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 coadministration of cortisol with L-arginine on plasma Larginine 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 Larginine per day (study 2). Co-administration of L-arginine 21 g/day with cortisol 80 mg/day did not prevent cortisolinduced increases in blood pressure or cortisol-induced falls in plasma nitrate/nitrite concentrations. Conclusion: 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.